135 results on '"Kim, Chang-Deok"'
Search Results
2. Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.
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Shin, Min-Jeong, Kim, Hyun-Sun, Lee, Pyeongan, Yang, Na-Gyeong, Kim, Jae-Yun, Eun, Yun-Su, Lee, Whiin, Kim, Doyeon, Lee, Young, Jung, Kyung-Eun, Hong, Dongkyun, Shin, Jung-Min, Lee, Sul-Hee, Lee, Sung-Yul, Kim, Chang-Deok, and Kim, Jung-Eun
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KERATINOCYTE differentiation ,TUMOR suppressor proteins ,SKIN inflammation ,REVERSE transcriptase polymerase chain reaction ,OXIDOREDUCTASES ,PROTEIN kinase C ,NF-kappa B ,TUMOR suppressor genes - Abstract
Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Establishment and evaluation of immortalized human epidermal keratinocytes for an alternative skin irritation test
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Kim, Cho-Won, Kim, Chang Deok, and Choi, Kyung-Chul
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- 2017
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4. Hyaluronic Acid Decreases Lipid Synthesis in Sebaceous Glands
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Jung, Yu Ra, Hwang, Chul, Ha, Jeong-Min, Choi, Dae-Kyoung, Sohn, Kyung-Cheol, Lee, Young, Seo, Young-Joon, Lee, Young-Ho, Kim, Chang-Deok, Lee, Jeung-Hoon, and Im, Myung
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- 2017
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5. Immortalization of human corneal epithelial cells using simian virus 40 large T antigen and cell characterization
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Kim, Cho-Won, Go, Ryeo-Eun, Lee, Geum-A, Kim, Chang Deok, Chun, Young-Jin, and Choi, Kyung-Chul
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- 2016
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6. Tropomyosin-receptor kinase fused gene (TFG) regulates lipid production in human sebocytes
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Choi, So-Ra, Hwang, Yul-Lye, Kim, Soo Jung, Sohn, Kyung-Cheol, Choi, Chong Won, Park, Kyung Duck, Lee, Young, Seo, Young-Joon, Lee, Jeung-Hoon, Hong, Seung-Phil, Seo, Seong Jun, Kim, Seong-Jin, and Kim, Chang Deok
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- 2019
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7. Induction of alopecia areata in C3H/HeJ mice using polyinosinic-polycytidylic acid (poly[I:C]) and interferon-gamma
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Shin, Jung-Min, Choi, Dae-Kyoung, Sohn, Kyung-Cheol, Koh, Jung-Woo, Lee, Young Ho, Seo, Young-Joon, Kim, Chang Deok, Lee, Jeung-Hoon, and Lee, Young
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- 2018
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8. Baricitinib Attenuates IFN-γ and Polyinosinic:polycytidylic Acid‒Induced Mitochondrial Damage and Inflammasome Activation in Human Keratinocytes
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Shin, Jung-Min, Lee, Young-Yoon, Hong, Dongkyun, Jung, Kyung-Eun, Seo, Young-Joon, Kim, Chang Deok, Yang, Hanseul, and Lee, Young
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- 2023
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9. The potential role of fibroblast‐derived multi‐peptide factors in activation of growth factors and β‐Catenin in hair follicle cells.
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Shin, Jung‐Min, Lee, Young‐Yoon, Kim, Kyung Min, Won, Kyung Shin, Suh, Sang Bum, Hong, Dongkyun, Jung, Kyung Eun, Kim, Chang‐Deok, Seo, Young‐Joon, Cho, Sung Bin, and Lee, Young
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VASCULAR endothelial growth factors ,INSULIN-like growth factor-binding proteins ,HAIR follicles ,EPIDERMAL growth factor ,KERATINOCYTE growth factors ,MINOXIDIL ,GROWTH factors - Abstract
Background: Dermal fibroblasts play a pivotal role in hair follicle regeneration during wound repair. Recently, dermal fibroblast‐conditioned medium (DFCM), which contains multi‐peptide factors (MPFs), has been used to promote wound repair. Aim: This study aimed to investigate the stimulatory effects of MPF‐containing DFCM on hair growth. Methods: MPF‐containing DFCM was prepared using human neonatal dermal fibroblasts. Outer root sheath (ORS) and dermal papilla (DP) cells were cultured in MPF‐containing DFCM. We examined the expression and secretion of growth factors and cytokines using quantitative polymerase chain reaction and a growth factor array. In addition, the effect of MPFs on β‐catenin activity was determined using the TOPflash assay. All experiments were repeated at least three times with separate batches of cells. Results: MPF‐containing DFCM increased keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) mRNA expression in ORS cells and KGF and VEGF mRNA expression in DP cells. When ORS cells were treated with MPF‐containing DFCM, the secretion of several growth factors, including EGF, VEGF, insulin‐like growth factor‐binding protein (IGFBP)‐4, IGFBP‐6, and fibroblast growth factor‐7, was increased in the cell‐cultured medium compared with that in control. Additionally, MPF‐containing DFCM increased the transcriptional activation of β‐catenin in DP cells. Conclusions: These results suggest that MPF‐containing DFCM might stimulate hair growth by inducing growth factors in ORS and DP cells and regulating β‐catenin in DP cells. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Augmentation of NAD+ by Dunnione Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.
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Lee, Seung Hoon, Kim, Hyung-Jin, Oh, Gi-Su, Lee, Su-Bin, Khadka, Dipendra, Cao, Wal, Choe, Seong-Kyu, Shim, Hyeok, Kim, Chang-Deok, Kwak, Tae Hwan, and So, Hong-Seob
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SKIN inflammation ,TOPICAL drug administration ,ENZYME-linked immunosorbent assay ,THERAPEUTICS ,SKIN diseases - Abstract
Background: Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of NAD
+ /NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-κB and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of NAD+ levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of NAD+ /NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice. Methods: Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-κB p65 and STAT3 was determined by Western blotting. Results: Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the NAD+ /NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23. Conclusion: Pharmacological modulation of cellular NAD+ levels could be a promising therapeutic approach for psoriasis-like skin disease. [ABSTRACT FROM AUTHOR]- Published
- 2022
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11. Expression of Neutrophil Gelatinase-Associated Lipocalin in Skin Epidermis
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Seo, Seong Jun, Ahn, Ji-Young, Hong, Chang-Kwun, Seo, Eun-Young, Kye, Kyung-Chae, Lee, Woong-Hee, Lee, Sang-Keun, Lim, Jong-Soon, Hahn, Myong-Joon, Kjeldsen, Lars, Borregaard, Niels, Kim, Chang Deok, Park, Jang-Kyu, and Lee, Jeung-Hoon
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- 2006
12. Molecular Cloning and Expression of Human Keratinocyte Proline-Rich Protein (hKPRP), an Epidermal Marker Isolated from Calcium-Induced Differentiating Keratinocytes
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Lee, Woong-Hee, Jang, Sunhyae, Lee, Jung-Suk, Lee, Young, Seo, Eun-Young, You, Kwan-Hee, Lee, Seung-Chul, Nam, Kwang-Il, Kim, Jin-Man, Kee, Sun-Ho, Yang, Jun-Mo, Seo, Young-Joon, Park, Jang-Kyu, Kim, Chang Deok, and Lee, Jeung-Hoon
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- 2005
13. Signaling Events During Induction of Plasminogen Activator Inhibitor-1 Expression by Sphingosylphosphorylcholine in Cultured Human Dermal Fibroblasts
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Kye, Kyung-Chae, Chae, Eun-Kyung, Piao, Yong-Jun, Park, Seonyang, Park, Jang-Kyu, Kim, Chang Deok, Lee, Jeung-Hoon, and Suhr, Ki-Beom
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- 2004
14. Roles of RNA-binding proteins in inflammatory skin diseases
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Kim, Chang Deok
- Abstract
RNA-binding proteins (RBPs) are proteins that bind RNA and regulate the fate and function of the bound RNAs. RBPs regulate the expression of target mRNA by modulating splicing, polyadenylation, localization, translation and decay. Specific RNA binding motifs, including AU-rich elements (AREs), GU-rich elements or polypyrimidine tracts, may interact with a variety of RBP, resulting in opposing mRNA fates such as stabilization or destabilization of target transcripts. Various inflammatory cytokine mRNAs contains RNA binding motifs within the 3u2032-untranslated region (UTR) and RPBs are important regulators of the immune response. In this study, we determined the roles of RBPs in inflammatory skin diseases such as psoriasis and alopecia areata. We targeted RPBs such as tristetraprolin (TTP), AU-binding factor 1 (AUF1), Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a), and Human antigen R (HuR). TTP and AUF1 promote mRNA degradation. Conversely Arid5a and HuR increase mRNA stability. First we examined the expression of RBPs in psoriasis and alopecia areata and also checked the expression of RBPs during PAMP-induced inflammation in keratinocytes. To further study the effects and mechanism of RBPs on innate immunity of keratinocytes, we conducted overexpression and knockdown of RBPs by transduction of adenoviruses and examined the effects on inflammatory responses in keratinocytes. Knockdown of Arid5a inhibited PAMP-induced inflammation in keratinocytes. These results provide a new mechanism to understand the pathogenesis of skin inflammatory diseases.
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- 2017
15. NQO1 suppresses the growth of cutaneous squamous cell carcinoma cells
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Kim, Chang Deok
- Abstract
Cutaneous squamous cell carcinoma (SCC) is an easily occurred cancer, which can worsen the quality of life considerably. It is known that external stimulus such as ultraviolet (UV) radiation induces cutaneous SCC via provoking oxidative stress. NAD(P)H dehydrogenase 1 (NQO1) is a ubiquitous flavoenzyme that functions as a guardian against oxidative stress. However, the effect of NQO1 on cutaneous SCC is not clearly elucidated. In this study, we investigated the effect of NQO1 on cutaneous SCC cells using the recombinant adenoviruses that can upregulate and/or downregulate NQO1 expression. Overexpression of NQO1 resulted in significant decrease of cell proliferation and colony forming activity of SCC lines (SCC12 and SCC13 cells). By contrast, knockdown of NQO1 increased the cell proliferation and colony forming activity. Accordingly, the levels of proliferation-related regulators, such as CDK4, CDK6, SOX2 and p63, were decreased by overexpression of NQO1, while those were increased by knockdown of NQO1. In addition, NQO1 affected the invasion and migration of SCC cells in a very similar way, with the regulation of epithelial-mesenchymal transition (EMT)-related molecules, including E-cadherin, N-cadherin, Vimentin, Snail and Slug. Finally, overexpression of NQO1 decreased the level of phosphorylated AKT, JNK and p38 MAPK, while knockdown of NQO1 increased the level of phosphorylated signaling molecules. Based on these data, NQO1 has tumor suppressive function in cutaneous SCC cells.
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- 2017
16. Role of Kruppel-like factor 4 (KLF4) in cutaneous squamous cell carcinoma
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Kim, Chang Deok
- Abstract
Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays a role in terminal differentiation of epidermal keratinocytes. There are conflicting reports regarding the role of KLF4 in tumor development, with both the tumor suppressive and/or oncogenic properties depending on different conditions and cell types. In this study, we investigated the functional importance of KLF4 in cutaneous squamous cell carcinoma (SCC). Immunohistochemistry showed that KLF4 expression was relatively lowin SCC lesion compared to normal epidermis. To examine the effects of KFL4, we transduced SCC lines (SCC12 and SCC13 cells) with the KLF4-expressing recombinant adenovirus. Overexpression of KLF4 significantly decreased cell proliferation and colony forming activity. In addition, overexpression of KLF4markedly reduced invasive potential, along with the downregulation of epithelial-mesenchymal transition (EMT)-related molecules. In a mechanistic study, KLF4 inhibited SOX2, of which expression is critical for tumor initiation and growth of SCC. Further investigations indicated that SOX2 expression isinduced by TGF-b/SMAD signaling, and that overexpression of KLF4 inhibited SMAD signaling via upregulation of SMAD7, an important inhibitory SMAD molecule. Based on these data, KLF4 plays a tumor suppressive role in cutaneous SCC cells.
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- 2017
17. Autophagy Suppresses Toll-Like Receptor 3-Mediated Inflammatory Reaction in Human Epidermal Keratinocytes.
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Li, Xue Mei, Jung, Kyung Eun, Yim, Su Hyuk, Hong, Dong Kyun, Kim, Chang Deok, Hong, Jeong Yeon, Lee, Ho Jung, Lee, Sung Yul, Kim, Jung Eun, and Park, Chang Wook
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AUTOPHAGY ,ANIMAL experimentation ,CELLS ,EPIDERMIS ,KERATINOCYTES ,MICE ,POLYMERS ,PSORIASIS ,QUINOLINE ,RAPAMYCIN ,TOLL-like receptors ,IN vitro studies - Abstract
Autophagy, one mechanism of programmed cell death, is fundamental to cellular homeostasis. Previous studies have identified autophagy as a novel mechanism by which cytokines control the immune response. However, its precise role in immune-related inflammatory skin diseases such as psoriasis remains unclear. Thus, this study explored the functional role of autophagy in psoriatic inflammation of epidermal keratinocytes. Strong light chain 3 immunoreactivity was observed in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model, and it was readily induced by polycytidylic acid (poly (I:C)), which stimulates Toll-like receptor 3 (TLR3), in human epidermal keratinocytes in vitro. Rapamycin-induced activation of autophagy significantly reduced poly (I:C)-induced inflammatory reaction, whereas, inhibition of autophagy by 3-methyladeine increased that. Our results indicate that the induction of autophagy may attenuate TLR3-mediated immune responses in human epidermal keratinocytes, thus providing novel insights into the mechanisms underlying the development of inflammatory skin diseases including psoriasis. [ABSTRACT FROM AUTHOR]
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- 2020
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18. Deficiency of Crif1 in hair follicle stem cells retards hair growth cycle in adult mice.
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Shin, Jung-Min, Ko, Jung-Woo, Choi, Chong-Won, Lee, Young, Seo, Young-Joon, Lee, Jeung-Hoon, and Kim, Chang-Deok
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HAIR growth ,HAIR follicles ,STEM cells ,HAIR cells ,MITOCHONDRIAL proteins ,MICE - Abstract
Hair growth is the cyclically regulated process that is characterized by growing phase (anagen), regression phase (catagen) and resting phase (telogen). Hair follicle stem cells (HFSCs) play pivotal role in the control of hair growth cycle. It has been notified that stem cells have the distinguished metabolic signature compared to differentiated cells, such as the preference to glycolysis rather than mitochondrial respiration. Crif1 is a mitochondrial protein that regulates the synthesis and insertion of oxidative phosphorylation (OXPHOS) polypeptides to inner membrane of mitochondria. Several studies demonstrate that tissue-specific knockout of Crif1 leads to mitochondrial dysfunction. In this study, we investigated the effect of mitochondrial dysfunction in terms of Crif1 deficiency on the hair growth cycle of adult mice. We created two kinds of inducible conditional knockout (icKO) mice. In epidermal specific icKO mice (Crif1 K14icKO), hair growth cycle was significantly retarded compared to wild type mice. Similarly, HFSC specific icKO mice (Crif1 K15icKO) showed significant retardation of hair growth cycle in depilation-induced anagen model. Interestingly, flow cytometry revealed that HFSC populations were maintained in Crif1 K15icKO mice. These results suggest that mitochondrial function in HFSCs is important for the progression of hair growth cycle, but not for maintenance of HFSCs. [ABSTRACT FROM AUTHOR]
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- 2020
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19. Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells.
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Zhang, Qing-Ling, Lian, De-De, Zhu, Ming Ji, Li, Xue Mei, Lee, Jae Kyung, Yoon, Tae-Jin, Lee, Jeung-Hoon, Jiang, Ri-Hua, and Kim, Chang Deok
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ANTHELMINTICS ,APOPTOSIS ,CELL lines ,CELLULAR signal transduction ,DOSE-effect relationship in pharmacology ,ENDOPLASMIC reticulum ,MOLECULAR structure ,SQUAMOUS cell carcinoma ,PHYSIOLOGICAL stress ,TRANSCRIPTION factors ,TRANSFERASES ,CASPASES ,CELL survival ,PHARMACODYNAMICS - Abstract
Drug repurposing and/or repositioning is an alternative method to develop new treatment for certain diseases. Albendazole was originally developed as an anthelmintic medication, and it has been used to treat a variety of parasitic infestations. In this study, we investigated the antitumor effect of albendazole and putative action mechanism. Results showed that albendazole dramatically decreased the cell viability of SCC cell lines (SCC12 and SCC13 cells). Albendazole increased apoptosis-related signals, including cleaved caspase-3 and PARP-1 in a dose-dependent fashion. The mechanistic study showed that albendazole induced endoplasmic reticulum (ER) stress, evidenced by increase of CHOP, ATF-4, caspase-4, and caspase-12. Pretreatment with ER stress inhibitor 4-PBA attenuated albendazole-induced apoptosis of SCC cells. In addition, albendazole decreased the colony-forming ability of SCC cells, together with inhibition of Wnt/β-catenin signaling. These results indicate that albendazole shows an antitumor effect via regulation of ER stress and cancer stemness, suggesting that albendazole could be repositioned for cutaneous SCC treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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20. Adiponectin Signaling Regulates Lipid Production in Human Sebocytes.
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Jung, Yu Ra, Lee, Jin-Hyup, Sohn, Kyung-Cheol, Lee, Young, Seo, Young-Joon, Kim, Chang-Deok, Lee, Jeung-Hoon, Hong, Seung-Phil, Seo, Seong-Jun, Kim, Seong-Jin, and Im, Myung
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ADIPONECTIN ,CELLULAR signal transduction ,LIPIDS ,INFLAMMATION ,PROTEIN expression - Abstract
Adiponectin plays important roles in metabolic function, inflammation and multiple biological activities in various tissues. However, evidence for adiponectin signaling in sebaceous glands is lacking, and its role remains to be clarified. This study investigated the role of adiponectin in lipid production in sebaceous glands in an experimental study of human sebocytes. We demonstrated that human sebaceous glands in vivo and sebocytes in vitro express adiponectin receptor and that adiponectin increased cell proliferation. Moreover, based on a lipogenesis study using Oil Red O, Nile red staining and thin layer chromatography, adiponectin strongly upregulated lipid production in sebocytes. In three-dimensional culture of sebocytes, lipid synthesis was markedly enhanced in sebocytes treated with adiponectin. This study suggested that adiponectin plays a significant role in human sebaceous gland biology. Adiponectin signaling is a promising target in the clinical management of barrier disorders in which sebum production is decreased, such as in atopic dermatitis and aged skin. [ABSTRACT FROM AUTHOR]
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- 2017
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21. Comparison of Vitamin D Levels in Patients with and without Acne: A Case-Control Study Combined with a Randomized Controlled Trial.
- Author
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Lim, Seul-Ki, Ha, Jeong-Min, Lee, Young-Ho, Lee, Young, Seo, Young-Joon, Kim, Chang-Deok, Lee, Jeung-Hoon, and Im, Myung
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ACNE ,IMMUNODEFICIENCY ,VITAMIN D deficiency ,CHOLECALCIFEROL ,BLOOD serum analysis ,THERAPEUTICS - Abstract
Background: Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases, including atopic dermatitis and psoriasis. Acne is a common inflammatory skin disease; however, the association with vitamin D remains unclear. Objectives: We evaluated vitamin D levels in patients with acne to determine the effect of vitamin D supplementation. Methods: This study included 80 patients with acne and 80 healthy controls. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured, and demographic data were collected. Vitamin D-deficient patients were treated with oral cholecalciferol at 1000 IU/day for 2 months. Results: Deficiency in 25(OH)D was detected in 48.8% of patients with acne, but in only 22.5% of the healthy controls. The level of 25(OH)D was inversely associated with the severity of acne, and there was a significant negative correlation with inflammatory lesions. In a subsequent trial, improvement in inflammatory lesions was noted after supplementation with vitamin D in 39 acne patients with 25(OH)D deficiency. Limitations: Limitations of the study include the small number of patients in the supplementation study and the natural fluctuation of acne. Conclusions: Vitamin D deficiency was more frequent in patients with acne, and serum 25(OH)D levels were inversely correlated with acne severity, especially in patients with inflammatory lesions. [ABSTRACT FROM AUTHOR]
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- 2016
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22. Nrf2 Negatively Regulates Melanogenesis by Modulating PI3K/Akt Signaling.
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Shin, Jung-Min, Kim, Mi Yoon, Sohn, Kyung-Cheol, Jung, So-Young, Lee, Hae-Eul, Lim, Jae Woo, Kim, Sooil, Lee, Young-Ho, Im, Myung, Seo, Young-Joon, Kim, Chang Deok, Lee, Jeung-Hoon, Lee, Young, and Yoon, Tae-Jin
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NF-kappa B ,MELANOGENESIS ,PHOSPHATIDYLINOSITOL 3-kinases ,PROTEIN kinase B ,OXIDATIVE stress ,XENOBIOTICS ,CYTOPROTECTION - Abstract
Nrf2 plays a role in protection of cells against oxidative stress and xenobiotic damage by regulating cytoprotective genes. In this study, we investigated the effect of Nrf2 on melanogenesis in normal human melanocytes (NHMCs). When NHMCs were transduced with a recombinant adenovirus expressing Nrf2, melanin synthesis was significantly decreased. Consistent with this result, overexpression of Nrf2 decreased the expression of tyrosinase and tyrosinase-related protein 1. The inhibitory effect of Nrf2 was reversed by overexpression of Keap1, an intracellular regulator of Nrf2. Interestingly, Nrf2 overexpression resulted in marked activation of PI3K/Akt signaling. Conversely, inhibition of PI3K activity by treatment with wortmannin reversed the depigmentary effects of Nrf2. Taken together, these results strongly suggest that Nrf2 negatively regulates melanogenesis by modulating the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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23. Imiquimod Induces Apoptosis of Squamous Cell Carcinoma (SCC) Cells via Regulation of A20.
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Sohn, Kyung-Cheol, Li, Zheng Jun, Choi, Dae-Kyoung, Zhang, Tiejun, Lim, Jae Woo, Chang, In-Kyu, Hur, Gang Min, Im, Myung, Lee, Young, Seo, Young-Joon, Lee, Jeung-Hoon, and Kim, Chang Deok
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CANCER treatment ,SQUAMOUS cell carcinoma ,APOPTOSIS ,CANCER cells ,NUCLEOSIDES ,TOLL-like receptors ,C-Jun N-terminal kinases - Abstract
Imiquimod, a nucleoside analogue of the imidazoquinoline family, is being used to treat various cutaneous cancers including squamous cell carcinoma (SCC). Imiquimod activates anti-tumor immunity via Toll-like receptor 7 (TLR7) in macrophage and other immune cells. Imiquimod can also affect tumor cells directly, regardless of its impact on immune system. In this study, we demonstrated that imiquimod induced apoptosis of SCC cells (SCC12) and A20 was involved in this process. When A20 was overexpressed, imiquimod-induced apoptosis was markedly inhibited. Conversely, knockdown of A20 potentiated imiquimod-induced apoptosis. Interestingly, A20 counteracted activation of c-Jun N-terminal kinase (JNK), suggesting that A20-regulated JNK activity was possible mechanism underlying imiquimod-induced apoptosis of SCC12 cells. Finally, imiquimod-induced apoptosis of SCC12 cells was taken place in a TLR7-independent manner. Our data provide new insight into the mechanism underlying imiquimod effect in cutaneous cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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24. Roles of TLR7 in Activation of NF-κB Signaling of Keratinocytes by Imiquimod.
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Li, Zheng Jun, Sohn, Kyung-Cheol, Choi, Dae-Kyoung, Shi, Ge, Hong, Dongkyun, Lee, Han-Eul, Whang, Kyu Uang, Lee, Young Ho, Im, Myung, Lee, Young, Seo, Young-Joon, Kim, Chang Deok, and Lee, Jeung-Hoon
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TOLL-like receptors ,NF-kappa B ,CELLULAR signal transduction ,KERATINOCYTES ,GENE expression ,INFLAMMATION ,CHEMOKINES ,PHYSIOLOGY - Abstract
Imiquimod is known to exert its effects through Toll-like receptor 7 (TLR7) and/or TLR8, resulting in expression of proinflammatory cytokines and chemokines. Keratinocytes have not been reported to constitutively express TLR7 and TLR8, and the action of imiquimod is thought to be mediated by the adenine receptor, not TLR7 or TLR8. In this study, we revealed the expression of TLR7 in keratinocytes after calcium-induced differentiation. After addition of calcium to cultured keratinocytes, the immunological responses induced by imiquimod, such as activation of NF-κB and induction of TNF-α and IL-8, were more rapid and stronger. In addition, imiquimod induced the expression TLR7, and acted synergistically with calcium to induce proinflammatory cytokines. We confirmed that the responses induced by imiquimod were significantly inhibited by microRNAs suppressing TLR7 expression. These results suggest that TLR7 expressed in keratinocytes play key roles in the activation of NF-κB signaling by imiquimod, and that their modulation in keratinocytes could provide therapeutic potential for many inflammatory skin diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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25. Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/β-Catenin Pathway Stimulation by Regulating GSK3b Activity.
- Author
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Kim, Jaeyoon, Shin, Jae Young, Choi, Yun-Ho, Lee, So Young, Jin, Mu Hyun, Kim, Chang Deok, Kang, Nae-Gyu, and Lee, Sanghwa
- Subjects
ADENOSINES ,CATENINS ,TISSUE remodeling ,TRANSFORMING growth factors-beta ,BONE morphogenetic proteins ,GLYCOGEN synthase kinase ,SOMATOMEDIN - Abstract
Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A
2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A , A2B and PKA. As a result of Wnt/β-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFβ) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/β-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds. [ABSTRACT FROM AUTHOR]- Published
- 2021
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26. Quercitrin Stimulates Hair Growth with Enhanced Expression of Growth Factors via Activation of MAPK/CREB Signaling Pathway.
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Kim, Jaeyoon, Kim, Soon Re, Choi, Yun-Ho, Shin, Jae young, Kim, Chang Deok, Kang, Nae-Gyu, Park, Byung Cheol, Lee, Sanghwa, Grant, George, and McPhee, Derek J.
- Subjects
HAIR growth ,GROWTH factors ,MITOGEN-activated protein kinases ,HAIR follicles ,MITOCHONDRIAL membranes ,MEMBRANE potential - Abstract
The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors—such as bFGF, KGF, PDGF-AA, and VEGF—were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway. [ABSTRACT FROM AUTHOR]
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- 2020
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27. Correction: Adiponectin Signaling Regulates Lipid Production in Human Sebocytes.
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Jung, Yu Ra, Lee, Jin-Hyup, Sohn, Kyung-Cheol, Lee, Young, Seo, Young-Joon, Zouboulis, Christos C., Kim, Chang-Deok, Lee, Jeung-Hoon, Hong, Seung-Phil, Seo, Seong-Jun, Kim, Seong-Jin, and Im, Myung
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ADIPONECTIN ,LIPID synthesis ,SEBACEOUS glands - Published
- 2017
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28. Targeted deletion of Crif1 in mouse epidermis impairs skin homeostasis and hair morphogenesis.
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Shin, Jung-Min, Choi, Dae-Kyoung, Sohn, Kyung-Cheol, Kim, Ji-Young, Im, Myung, Lee, Young, Seo, Young-Joon, Shong, Minho, Lee, Jeung-Hoon, and Kim, Chang Deok
- Abstract
The epidermis, which consists mainly of keratinocytes, acts as a physical barrier to infections by regulating keratinocyte proliferation and differentiation. Hair follicles undergo continuous cycling to produce new one. Therefore, optimum supply of energy from the mitochondria is essential for maintaining skin homeostasis and hair growth. CRIF1 is a mitochondrial protein that regulates mitoribosome-mediated synthesis and insertion of mitochondrial oxidative phosphorylation polypeptides into the mitochondrial membrane in mammals. Recent studies reveal that conditional knockout (cKO) of Crif1 in specific tissues of mice induced mitochondrial dysfunction. To determine whether the mitochondrial function of keratinocytes affects skin homeostasis and hair morphogenesis, we generated epidermis-specific Crif1 cKO mice. Deletion of Crif1 in epidermis resulted in impaired mitochondrial function and Crif1 cKO mice died within a week. Keratinocyte proliferation and differentiation were markedly inhibited in Crif1 cKO mice. Furthermore, hair follicle morphogenesis of Crif1 cKO mice was disrupted by down-regulation of Wnt/β-catenin signaling. These results demonstrate that mitochondrial function in keratinocytes is essential for maintaining epidermal homeostasis and hair follicle morphogenesis. [ABSTRACT FROM AUTHOR]
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- 2017
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29. Involvement of PKCδ in radiation-resistance of human non small cell lung cancer cell line.
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Cho, Moon-June, Lee, Young-Sook, Mollah, Mohammad Lalmoddin, Kim, Chang Deok, Lee, Jeung-Hoon, Yeo, Seung-Gu, and Kim, Jun-Sang
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- 2007
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30. Propionibacterium acnes Activates the NLRP3 Inflammasome in Human Sebocytes.
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Li, Zheng Jun, Choi, Dae Kyoung, Sohn, Kyung Cheol, Seo, Min Seok, Lee, Hae Eul, Lee, Young, Seo, Young Joon, Lee, Young Ho, Shi, Ge, Zouboulis, Christos C, Kim, Chang Deok, Lee, Jeung Hoon, and Im, Myung
- Subjects
- *
CUTIBACTERIUM acnes , *SEBACEOUS glands , *BIOFILMS , *PROPIONIBACTERIUM , *CUTANEOUS glands , *STERNAL gland - Abstract
Propionibacterium acne and sebaceous glands are considered to have an important role in the development of acne. Although information regarding the activation of innate immunity by P. acnes in the sebaceous gland is limited, different P. acnes phylotypes and a higher prevalence of follicular P. acnes macrocolonies/biofilms in sebaceous follicles of skin biopsies from acne compared with control skin and occasionally single P. acnes clusters in single sebaceous glands have been detected. In this study, we investigated whether P. acnes activates the inflammasome in human sebaceous glands in vivo and in vitro. We found that IL-1β expression was upregulated in sebaceous glands of acne lesions. After stimulation of human sebocytes with P. acnes, the activation of caspase-1 and secretion of IL-1β were enhanced significantly. Moreover, knocking down the expression of NLRP3 abolished P. acnes-induced IL-1β production in sebocytes. The activation of the NLRP3 inflammasome by P. acnes was dependent on protease activity and reactive oxygen species generation. Finally, we found that NALP3-deficient mice display an impaired inflammatory response to P. acnes. These results suggest that human sebocytes are important immunocompetent cells that induce the NLRP3 inflammasome, and that P. acnes-induced IL-1β activation in sebaceous glands may have a role in combating skin infections and in acne pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2014
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31. Regional Difference of Inflammatory Acne Lesions According to β-Defensin-2 Expression.
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Choi, Dae Kyoung, Li, Zheng Jun, Chang, In Kyu, Sohn, Kyung Cheol, Lee, Young, Seo, Young Joon, Lee, Young Ho, Shi, Ge, Kim, Chang Deok, Lee, Jeung Hoon, and Im, Myung
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- *
ACNE , *DEFENSINS - Abstract
A letter to the editor is presented which discusses a study on inflammatory acne lesions' regional differences based on the facial topography and β-defensin-2 expression.
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- 2014
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32. Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.
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Shin MJ, Kim HS, Lee P, Yang NG, Kim JY, Eun YS, Lee W, Kim D, Lee Y, Jung KE, Hong D, Shin JM, Lee SH, Lee SY, Kim CD, and Kim JE
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- Animals, Humans, Mice, Disease Models, Animal, Inflammation, NF-kappa B, Tumor Suppressor Proteins genetics, WW Domain-Containing Oxidoreductase genetics, Dermatitis, Psoriasis chemically induced, Psoriasis genetics
- Abstract
Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.
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- 2023
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33. Pitavastatin Induces Apoptosis of Cutaneous Squamous Cell Carcinoma Cells through Geranylgeranyl Pyrophosphate-Dependent c-Jun N-Terminal Kinase Activation.
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Kim KI, Kim SM, Lee YY, Lee Y, Kim CD, and Yoon TJ
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Background: Pitavastatin is a cholesterol-lowering drug and is widely used clinically. In addition to this effect, pitavastatin has shown the potential to induce apoptosis in cutaneous squamous cell carcinoma (SCC) cells., Objective: The purpose of this study is to investigate the effects and possible action mechanisms of pitavastatin., Methods: SCC cells (SCC12 and SCC13 cells) were treated with pitavastatin, and induction of apoptosis was confirmed by Western blot. To examine whether pitavastatin-induced apoptosis is related to a decrease in the amount of intermediate mediators in the cholesterol synthesis pathway, the changes in pitavastatin-induced apoptosis after supplementation with mevalonate, squalene, geranylgeranyl pyrophosphate (GGPP) and dolichol were investigated., Results: Pitavastatin dose-dependently induced apoptosis of cutaneous SCC cells, but the viability of normal keratinocytes was not affected by pitavastatin at the same concentrations. In supplementation experiments, pitavastatin-induced apoptosis was inhibited by the addition of mevalonate or downstream metabolite GGPP. As a result of examining the effect on intracellular signaling, pitavastatin decreased Yes1 associated transcriptional regulator and Ras homolog family member A and increased Rac family small GTPase 1 and c-Jun N-terminal kinase (JNK) activity. All these effects of pitavastatin on signaling molecules were restored when supplemented with either mevalonate or GGPP. Furthermore, pitavastatin-induced apoptosis of cutaneous SCC cells was inhibited by a JNK inhibitor., Conclusion: These results suggest that pitavastatin induces apoptosis of cutaneous SCC cells through GGPP-dependent JNK activation., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
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- 2023
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34. Screening of Plant-Derived Natural Extracts to Identify a Candidate Extract Capable of Enhancing Lipid Synthesis in Keratinocytes.
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Lee SH, Seo HS, Seo SJ, Kim CD, and Hong SP
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Background: Reduced lipid content in the stratum corneum is a major cause of skin-barrier dysfunction in various pathological conditions. Promoting lipid production is a potential strategy to improve skin-barrier function. Recent evidence supports the beneficial effects of adiponectin on lipid metabolism and senescence in keratinocytes., Objective: This study aimed to investigate whether plant extracts can enhance skin-barrier function., Methods: We screened fruit and herb extracts that enhance the lipid synthesis of keratinocytes via AMP-activated protein kinase (AMPK) activation and SIRT1 signaling in the adiponectin pathway. The levels of major lipid synthesis enzymes and transcription factors as well as epidermal barrier lipids involved in adiponectin-associated epidermal barrier formation were evaluated in the herbal extracts- or adiponectin-treated human epidermal keratinocyte and equivalent models. The mRNA expression of major lipid synthesis enzymes increased following treatment with Lycii Fructus , Prunus tomentosa , and Melia toosendan extracts., Results: The expression of transcription factors SIRT1, liver X receptor α, peroxisome proliferator-activated receptors (PPARs), and sterol regulatory element-binding proteins (SREBPs) were upregulated. Levels of free fatty acids, cholesterol, and ceramides were elevated. The expression of keratinocyte differentiation markers increased. In particular, among fruit extracts with a detectable effect, Melia toosendan induced the highest expression of lipid synthase., Conclusion: These results indicate that Melia toosendan is a promising candidate for improving skin-barrier function., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
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- 2022
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35. Augmentation of NAD + by Dunnione Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.
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Lee SH, Kim HJ, Oh GS, Lee SB, Khadka D, Cao W, Choe SK, Shim H, Kim CD, Kwak TH, and So HS
- Abstract
Background: Dunnione has anti-inflammatory properties arising from its ability to alter the ratio of NAD
+ /NADH through NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action, followed by subsequent inhibition of NF-κB and inflammatory cytokines. Psoriasis is a chronic, inflammatory skin disorder in which the IL-23/Th17 axis plays an important role in inflammation. However, it is unclear whether modulation of NAD+ levels affects psoriasis, such as skin inflammation. Therefore, in this study, we investigated the effect of NAD+ /NADH ratio modulation on imiquimod (IMQ)-induced, psoriasis-like skin inflammation in mice., Methods: Psoriasis-like skin inflammation was generated by daily topical application of IMQ cream. The severity of dermatitis was assessed using the Psoriasis Area Severity Index (PASI) and histochemistry. Expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay and quantitative PCR. Acetylation of NF-κB p65 and STAT3 was determined by Western blotting., Results: Dunnione improved IMQ-induced epidermal hyperplasia and inflammation, consistent with decreased levels of inflammatory cytokines (IL-17, IL-22, and IL-23) in skin lesions. Moreover, we found that an increase in the NAD+ /NADH ratio by dunnione restored SIRT1 activity, thereby reduced imiquimod-induced STAT3 acetylation, which modulates the expression of psoriasis-promoting inflammatory cytokines, such as IL-17, IL-22, and IL-23., Conclusion: Pharmacological modulation of cellular NAD+ levels could be a promising therapeutic approach for psoriasis-like skin disease., Competing Interests: Hong-Seob So is an employee of NADIANBIO Ltd. The author reports no other potential conflicts of interest in this work., (© 2022 Lee et al.)- Published
- 2022
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36. Role of Substance P in Regulating Micro-Milieu of Inflammation in Alopecia Areata.
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Kim C, Shin JM, Kim D, Park S, Hong D, Jung KE, Kim CD, Seo YJ, and Lee Y
- Abstract
Background: Alopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis., Objective: We aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells., Methods: We compared the serum levels of SP in 58 AA patients and 28 healthy subjects. Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining. Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growth-related factors in ORS cells., Results: SP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic., Conclusion: SP triggered a localized micro-inflammation in lesional hair follicles, provoked an inflammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
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- 2022
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37. Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts.
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Kim KI, Kwon CI, Lee JH, Kim CD, and Yoon TJ
- Abstract
Background: Fibroblasts produce collagen molecules that support the structure of the skin. The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars., Objective: The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts., Methods: Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot., Results: Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability., Conclusion: These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2022
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38. Activation of NLRP3 Inflammasome by Palmitic Acid in Human Sebocytes.
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Jung YR, Shin JM, Kim CH, Kim S, Kim CD, Seo YJ, Lee JH, Im M, Lee Y, and Lee YH
- Abstract
Background: Sebocytes are the main cells involved in the pathogenesis of acne by producing lipids and inflammatory cytokines. Although palmitic acid (PA) has been suggested to induce an inflammatory reaction, its effect on sebocytes remains to be elucidated., Objective: In the present study, we investigated whether PA promotes inflammasome-mediated inflammation of sebocytes both in vivo and in vitro ., Methods: We intradermally injected PA into the mice ears. And, we treated cultured human sebocytes with PA. Inflammasome-mediated inflammation was verified by immunohistochemistry, Western blot and ELISA., Results: PA-treated mice developed an inflammatory response associated with increased interleukin (IL)-1β expression in the sebaceous glands. When PA was added to cultured human sebocytes, caspase-1 activation and IL-1β secretion were significantly enhanced. In addition, NLRP3 knockdown attenuated IL-1β production by sebocytes stimulated with PA. PA-mediated inflammasome activation required reactive oxygen species., Conclusion: These findings indicate that PA activates the NLRP3 inflammasome before induction of an inflammatory response in sebocytes. Thus, PA may play a role in the inflammation of acne., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2021
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39. Azidothymidine Downregulates Insulin-Like Growth Factor-1 Induced Lipogenesis by Suppressing Mitochondrial Biogenesis and Mitophagy in Immortalized Human Sebocytes.
- Author
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Yoo JG, Li XM, Lee JK, Park S, Hong D, Jung KE, Lee Y, Seo YJ, Kim CD, Shin JM, and Choi CW
- Abstract
Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile., Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulinlike growth factor (IGF)-1-induced lipid synthesis in sebocytes., Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated., Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptorgamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes., Conclusion: These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes., Competing Interests: CONFLICTS OF INTEREST: The contents of this study have been used to apply for a patent application to the Korean Intellectual Property Office (Application number: 10-2019-0149751)., (Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2021
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40. Potential Role of Cytosolic RNA Sensor MDA5 as an Inhibitor for Keratinocyte Differentiation in the Pathogenesis of Psoriasis.
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Hong DK, Choi MR, Hwang YL, Lee JK, Lee Y, Seo YJ, Kim S, Lee YH, Kim CD, and Lee JH
- Abstract
Background: Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood., Objective: The purpose of this study is to uncover possible roles of MDA5 in psoriasis., Methods: Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus., Results: As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes., Conclusion: These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2021
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41. Possible Role of Lysine Demethylase 2A in the Pathophysiology of Psoriasis.
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Kim DH, Choi MR, Lee JK, Hong DK, Jung KE, Choi CW, Lee Y, Kim CD, Seo YJ, and Lee JH
- Abstract
Background: Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed., Objective: The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis., Methods: We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model., Results: Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis., Conclusion: Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2020 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2020
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42. Tumor Suppressive Function of NQO1 in Cutaneous Squamous Cell Carcinoma (SCC) Cells.
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Zhang QL, Li XM, Lian DD, Zhu MJ, Yim SH, Lee JH, Jiang RH, and Kim CD
- Subjects
- Carcinoma, Squamous Cell metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation genetics, Epithelial-Mesenchymal Transition drug effects, Epithelial-Mesenchymal Transition genetics, Humans, Signal Transduction drug effects, Signal Transduction genetics, Skin Neoplasms metabolism, Carcinoma, Squamous Cell genetics, Gene Expression Regulation, Neoplastic genetics, NAD(P)H Dehydrogenase (Quinone) genetics, NAD(P)H Dehydrogenase (Quinone) metabolism, NAD(P)H Dehydrogenase (Quinone) pharmacology, Skin Neoplasms genetics
- Abstract
Cutaneous squamous cell carcinoma (SCC) is a common cancer that significantly decreases the quality of life. It is known that external stimulus such as ultraviolet (UV) radiation induces cutaneous SCC via provoking oxidative stress. NAD(P)H dehydrogenase 1 (NQO1) is a ubiquitous flavoenzyme that functions as a guardian against oxidative stress. However, the effect of NQO1 on cutaneous SCC is not clearly elucidated. In this study, we investigated the effect of NQO1 on cutaneous SCC cells using the recombinant adenoviruses that can upregulate and/or downregulate NQO1 expression. Overexpression of NQO1 resulted in significant decrease of cell proliferation and colony forming activity of SCC lines (SCC12 and SCC13 cells). By contrast, knockdown of NQO1 increased the cell proliferation and colony forming activity. Accordingly, the levels of proliferation-related regulators, such as Cyclin D1, Cyclin E, PCNA, SOX2, and p63, were decreased by the overexpression of NQO1, while those were increased by knockdown of NQO1. In addition, NQO1 affected the invasion and migration of SCC cells in a very similar way, with the regulation of epithelial-mesenchymal transition- (EMT-) related molecules, including E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Finally, the overexpression of NQO1 decreased the level of phosphorylated AKT, JNK, and p38 MAPK, while the knockdown of NQO1 increased the level of phosphorylated signaling molecules. Based on these data, NQO1 has tumor suppressive function in cutaneous SCC cells., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Qing-Ling Zhang et al.)
- Published
- 2019
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43. Clinical Relevance for Serum Cold-Inducible RNA-Binding Protein Level in Alopecia Areata.
- Author
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Shin JM, Ko JW, Kwon IS, Choi JW, Hong D, Lee JH, Seo YJ, Kim CD, Lee JH, Lee Y, and Park KD
- Abstract
Background: Alopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cold stress, and has been identified as a damage-associated molecular pattern (DAMP) molecule that triggers the inflammatory response. Recent studies have shown that high-mobility group box 1, another DAMP molecule, is elevated in serum and scalp tissue of AA patients, suggesting a relationship between DAMP molecules and the pathogenesis of AA., Objective: To investigate the clinical significance of serum CIRP levels in AA., Methods: The serum levels of CIRP were compared between 68 patients with AA and 20 healthy controls. Additionally, the correlation between CIRP level and various clinical parameters was evaluated., Results: The serum CIRP levels were significantly higher in AA patients compared to healthy subjects. Moreover, there was an association between the serum CIRP level and clinical characteristics, such as disease duration and disease activity. However, there was no significant difference in the serum CIRP level among the clinical types of AA (AA multiplex, alopecia totalis, and alopecia universalis)., Conclusion: These results suggest that CIRP may play a significant role in the pathogenesis of AA and could be a potential biologic marker for monitoring the disease activity of AA., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2019 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2019
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44. Inhibition of Insulin-Like Growth Factor-1-Induced Sebum Production by Bilobetin in Cultured Human Sebocytes.
- Author
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Wang C, Hwang YL, Li XM, Kim SJ, Zhu MJ, Lee JH, Jiang RH, and Kim CD
- Abstract
Background: Sebocytes are the major cells of sebaceous gland. The essential role of sebocytes is the production of sebum, a specific lipid mixture, that covers the body surface and provides the barrier function. At puberty, sebum production increases under the effects of various stimuli including androgens and insulin-like growth factor-1 (IGF-1). Excessive sebum production changes the microenvironment surrounding hair follicle, often leading to the onset of acne., Objective: We previously performed screening test using cultured human sebocytes, and found that bilobetin had a potential for inhibiting lipid production. The aim of this study is to demonstrate the effects of bilobetin on IGF-1-induced lipogenesis in sebocytes., Methods: We pretreated simian virus 40 T (SV40T)-transformed sebocytes with bilobetin then stimulated with IGF-1. Effects of bilobetin on lipogenesis of sebocytes were examined by thin layer chromatography and Western blot., Results: Bilobetin markedly inhibited IGF-1-induced lipid production in sebocytes, especially in terms of production of squalene and wax ester. Supporting these results, bilobetin showed significant inhibitory effect on squalene synthase promoter activity. In addition, bilobetin significantly down-regulated lipogenic transcription factors such as sterol response element binding protein (SREBP)-1 and SREBP-2. To delineate the possible action mechanism, we investigated the effect of bilobetin on intracellular signaling. As a result, bilobetin inhibited IGF-1-induced phosphorylation of AKT., Conclusion: Together, these results suggest that bilobetin has an inhibitory potential on sebum production in sebocytes, being applicable for acne treatment., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2019 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2019
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45. Inhibition of Poly(I:C)-Induced Inflammation by Salvianolic Acid A in Skin Keratinocytes.
- Author
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Zhang QL, Jiang RH, Li XM, Ko JW, Kim CD, Zhu MJ, and Lee JH
- Abstract
Background: Skin keratinocytes participate actively in inducing immune responses when external pathogens are introduced, thereby contributing to elimination of pathogens. However, in condition where the excessive inflammation is occurred, chronic skin disease such as psoriasis can be provoked., Objective: We tried to screen the putative therapeutics for inflammatory skin disease, and found that salvianolic acid A (SAA) has an inhibitory effect on keratinocyte inflammatory reaction. The aim of this study is to demonstrate the effects of SAA in poly(I:C)-induced inflammatory reaction in skin keratinocytes., Methods: We pre-treated keratinocytes with SAA then stimulated with poly(I:C). Inflammatory reaction of keratinocytes was verified using real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot., Results: When skin keratinocytes were pre-treated with SAA, it significantly inhibited poly (I:C)-induced expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and CCL20. SAA inhibited poly(I:C)-induced activation of nuclear factor-κB signaling. And SAA also inhibited inflammasome activation, evidenced by decrease of IL-1β secretion. Finally, SAA markedly inhibited poly(I:C)-induced NLRP3 expression., Conclusion: These results demonstrate that SAA has an inhibitory effect on poly(I:C)-induced inflammatory reaction of keratinocytes, suggesting that SAA can be developed for the treatment of inflammatory skin diseases such as psoriasis., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2019 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2019
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46. Adiponectin Attenuates the Inflammation in Atopic Dermatitis-Like Reconstructed Human Epidermis.
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Seo HS, Seong KH, Kim CD, Seo SJ, Park BC, Kim MH, and Hong SP
- Abstract
Background: Atopic dermatitis (AD) is a chronic disorder, with a vicious cycle of repetitive inflammation and deterioration of the epidermal barrier function. Adiponectin, an adipokine, has anti-inflammatory effects on various metabolic and inflammatory disorders. Recently, its level was found to be reduced in serum and tissue samples from AD patients., Objective: We aimed to investigate the effects of adiponectin on epidermal inflammation and barrier structures in AD skin., Methods: A three-dimensional in vitro epidermal equivalent model mimicking AD was obtained by adding an inflammatory substance cocktail to normal human epidermal equivalents (HEEs). The expression of epidermal differentiation markers, primary inflammatory mediators, and lipid biosynthetic enzymes was compared between adiponectintreated AD-HEEs, untreated control AD-HEEs, and normal HEEs., Results: Adiponectin co-treatment 1) inhibited the increase in mRNA expression of major inflammatory mediators (carbonic anhydrase II, neuron-specific NEL-like protein 2, thymic stromal lymphopoietin, interleukin-8, tumor necrosis factor-alpha, and human beta-defensin-2) from keratinocytes in AD-inflammatory HEEs, 2) enhanced the expression of lipid biosynthetic enzymes (fatty acid synthase, HMG CoA reductase, and serine-palmitoyl transferase), and 3) promoted the expression of differentiation factors, especially filaggrin. We also found that the expression of adiponectin receptor-1 and -2 decreased in the epidermis of chronic AD lesion., Conclusion: Activation of the adiponectin pathway is expected to enhance epidermal differentiation and barrier function as well as attenuate inflammatory response to AD as a therapeutic approach., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2019 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2019
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47. Erratum: Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation.
- Author
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Choi MR, Shin JM, Shin YA, Chang YH, Chang MY, Lim CA, Sohn KC, Seo YJ, Kim CD, Lee JH, and Lee Y
- Abstract
[This corrects the article on p. 432 in vol. 30, PMID: 30065583.]., (Copyright © 2018 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2018
- Full Text
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48. Possible Role of Single Stranded DNA Binding Protein 3 on Skin Hydration by Regulating Epidermal Differentiation.
- Author
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Choi MR, Shin JM, Shin YA, Chang YH, Chang MY, Lim CA, Sohn KC, Seo YJ, Kim CD, Lee JH, and Lee Y
- Abstract
Background: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted., Objective: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function., Methods: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro., Results: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased., Conclusion: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.
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- 2018
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49. Three Streams for the Mechanism of Hair Graying.
- Author
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Jo SK, Lee JY, Lee Y, Kim CD, Lee JH, and Lee YH
- Abstract
Hair graying is an obvious sign of human aging. Although graying has been investigated extensively, the mechanism remains unclear. Here, we reviewed previous studies on the mechanism of graying and seek to offer some new insights. The traditional view is that hair graying is caused by exhaustion of the pigmentary potential of the melanocytes of hair bulbs. Melanocyte dysfunction may be attributable to the effects of toxic reactive oxygen species on melanocyte nuclei and mitochondria. A recent study suggests that bulge melanocyte stem cells (MSCs) are the key cells in play. Graying may be caused by defective MSC self-maintenance, not by any deficiency in bulbar melanocytes. Our previous study suggested that graying may be principally attributable to active hair growth. Active hair growth may produce oxidative or genotoxic stress in hair bulge. These internal stress may cause eventually depletion of MSC in the hair follicles. Taken together, hair graying may be caused by MSC depletion by genotoxic stress in the hair bulge. Hair graying may also be sometimes caused by dysfunction of the melanocytes by oxidative stress in the hair bulb. In addition, hair graying may be attributable to MSC depletion by active hair growth., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.
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- 2018
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50. Isoginkgetin Inhibits Insulin-Like Growth Factor-1-Induced Sebum Production in Cultured Human Sebocytes.
- Author
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Hwang YL, Lee MH, Oh HI, Kim HJ, Lim CA, Lee JH, and Kim CD
- Abstract
Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.
- Published
- 2018
- Full Text
- View/download PDF
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