5 results on '"Ae-Rang Hwang"'
Search Results
2. Inhibition of p90RSK Ameliorates PDGF-BB-Mediated Phenotypic Change of Vascular Smooth Muscle Cell and Subsequent Hyperplasia of Neointima
- Author
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Ae-Rang Hwang, Hee-Jung Lee, Suji Kim, Seong-Hee Park, and Chang-Hoon Woo
- Subjects
Inorganic Chemistry ,p90 ribosomal S6 kinase (p90RSK) ,platelet-derived growth factor (PDGF) ,vascular smooth muscle cell (VSMC) ,neointima formation ,Organic Chemistry ,General Medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Platelet-derived growth factor type BB (PDGF-BB) regulates vascular smooth muscle cell (VSMC) migration and proliferation, which play critical roles in the development of vascular conditions. p90 ribosomal S6 kinase (p90RSK) can regulate various cellular processes through many different target substrates in several cell types, but the regulatory function of p90RSK on PDGF-BB-mediated cell migration and proliferation and subsequent vascular neointima formation has not yet been extensively examined. In this study, we investigated whether p90RSK inhibition protects VSMCs against PDGF-BB-induced cellular phenotypic changes and the molecular mechanisms underlying the effect of p90RSK inhibition on neointimal hyperplasia in vivo. Pretreatment of cultured primary rat VSMCs with FMK or BI-D1870, which are specific inhibitors of p90RSK, suppressed PDGF-BB-induced phenotypic changes, including migration, proliferation, and extracellular matrix accumulation, in VSMCs. Additionally, FMK and BI-D1870 repressed the PDGF-BB-induced upregulation of cyclin D1 and cyclin-dependent kinase-4 expression. Furthermore, p90RSK inhibition hindered the inhibitory effect of PDGF-BB on Cdk inhibitor p27 expression, indicating that p90RSK may induce VSMC proliferation by regulating the G0/G1 phase. Notably, treatment with FMK resulted in attenuation of neointima development in ligated carotid arteries in mice. The findings imply that p90RSK inhibition mitigates the phenotypic switch and neointimal hyperplasia induced by PDGF-BB. more...
- Published
- 2023
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- View/download PDF
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3. CHIP Haploinsufficiency Exacerbates Hepatic Steatosis via Enhanced TXNIP Expression and Endoplasmic Reticulum Stress Responses
- Author
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Jung-Hwa Han, Dae-Hwan Nam, Seon-Hui Kim, Ae-Rang Hwang, So-Young Park, Jae Hyang Lim, and Chang-Hoon Woo
- Subjects
thioredoxin-interacting protein (TXNIP) ,Physiology ,Clinical Biochemistry ,endoplasmic reticulum (ER) stress ,Cell Biology ,metabolic disease ,Molecular Biology ,Biochemistry ,non-alcoholic fatty liver disease (NAFLD) ,carboxyl terminus of the Hsc70-interacting protein (CHIP) - Abstract
TXNIP is a critical regulator of glucose homeostasis, fatty acid synthesis, and cholesterol accumulation in the liver, and it has been reported that metabolic diseases, such as obesity, atherosclerosis, hyperlipidemia, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD), are associated with endoplasmic reticulum (ER) stress. Because CHIP, an E3 ligase, was known to be involved in regulating tissue injury and inflammation in liver, its role in regulating ER stress-induced NAFLD was investigated in two experimental NAFLD models, a tunicamycin (TM)-induced and other diet-induced NAFLD mice models. In the TM-induced NAFLD model, intraperitoneal injection of TM induced liver steatosis in both CHIP+/+ and CHIP+/− mice, but it was severely exacerbated in CHIP+/− mice compared to CHIP+/+ mice. Key regulators of ER stress and de novo lipogenesis were also enhanced in the livers of TM-inoculated CHIP+/− mice. Furthermore, in the diet-induced NAFLD models, CHIP+/− mice developed severely impaired glucose tolerance, insulin resistance and hepatic steatosis compared to CHIP+/+ mice. Interestingly, CHIP promoted ubiquitin-dependent degradation of TXNIP in vitro, and inhibition of TXNIP was further found to alleviate the inflammation and ER stress responses increased by CHIP inhibition. In addition, the expression of TXNIP was increased in mice deficient in CHIP in the TM- and diet-induced models. These findings suggest that CHIP modulates ER stress and inflammatory responses by inhibiting TXNIP, and that CHIP protects against TM- or HF–HS diet-induced NAFLD and serves as a potential therapeutic means for treating liver diseases. more...
- Published
- 2023
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4. Apelin-13 Inhibits Methylglyoxal-Induced Unfolded Protein Responses and Endothelial Dysfunction via Regulating AMPK Pathway
- Author
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Ae-Rang Hwang, Hyoung Chul Choi, Ji-Yun Lee, Sujin Kim, Chang-Hoon Woo, and Suji Kim
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UPR unfolded protein response ,AMPK ,0301 basic medicine ,Apoptosis ,Vasodilation ,030204 cardiovascular system & hematology ,endothelial dysfunction ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,methylglyoxal ,Endothelial dysfunction ,lcsh:QH301-705.5 ,Cells, Cultured ,Spectroscopy ,Methylglyoxal ,unfolded protein response ,General Medicine ,Endoplasmic Reticulum Stress ,Pyruvaldehyde ,Computer Science Applications ,Apelin ,Cell biology ,apelin ,Intercellular Signaling Peptides and Proteins ,Cell Survival ,MAP Kinase Signaling System ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,Endothelium ,Physical and Theoretical Chemistry ,Molecular Biology ,Dose-Response Relationship, Drug ,Endoplasmic reticulum ,Organic Chemistry ,medicine.disease ,Oxidative Stress ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,Unfolded protein response ,Reactive Oxygen Species - Abstract
It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction than glucose itself. Recent reports showed that high glucose and MGO induced endoplasmic reticulum (ER) stress and myocyte apoptosis in ischemic heart disease was inhibited by apelin. The goal of the study is to investigate the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress in endothelial cells, and to examine whether apelin-13, a cytoprotective polypeptide ligand, protects MGO-induced aortic endothelial dysfunction. MGO-induced ER stress and apoptosis were determined by immunoblotting and MTT assay in HUVECs. Aortic endothelial dysfunction was addressed by en face immunostaining and acetylcholine-induced vasodilation analysis with aortic rings from mice treated with MGO in the presence or absence of apelin ex vivo. TUDCA, an inhibitor of ER stress, inhibited MGO-induced apoptosis and reduction of cell viability, suggesting that MGO signaling to endothelial apoptosis is mediated via ER stress, which leads to activation of unfolded protein responses (UPR). In addition, MGO-induced UPR and aortic endothelial dysfunction were significantly diminished by apelin-13. Finally, this study showed that apelin-13 protects MGO-induced UPR and endothelial apoptosis through the AMPK pathway. Apelin-13 reduces MGO-induced UPR and endothelial dysfunction via regulating the AMPK activating pathway, suggesting the therapeutic potential of apelin-13 in diabetic cardiovascular complications. more...
- Published
- 2020
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5. ERK5 regulates basic fibroblast growth factor-induced type 1 plasminogen activator inhibitor expression and cell proliferation in lung fibroblasts
- Author
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Ae-Rang Hwang, Suji Kim, Dae-Hwan Nam, Jung-Hwa Han, Chang-Hoon Woo, Hyoung Chul Choi, and Jae Hyang Lim
- Subjects
Mef2 ,Pulmonary Fibrosis ,Basic fibroblast growth factor ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,chemistry.chemical_compound ,Mice ,Fibrosis ,Plasminogen Activator Inhibitor 1 ,Serpin E2 ,medicine ,Animals ,Humans ,MTT assay ,General Pharmacology, Toxicology and Pharmaceutics ,RNA, Small Interfering ,Fibroblast ,Promoter Regions, Genetic ,Lung ,Mitogen-Activated Protein Kinase 7 ,Cell Proliferation ,Reporter gene ,Cell growth ,MEF2 Transcription Factors ,General Medicine ,Fibroblasts ,medicine.disease ,Cell biology ,medicine.anatomical_structure ,chemistry ,Gene Expression Regulation ,Cell culture ,cardiovascular system ,Fibroblast Growth Factor 2 - Abstract
Aims bFGF is a potent mitogen of cells associated with fibrosis. Although ERK5 has been reported to play roles in the development of fibrosis, its roles in regulating bFGF-induced fibrotic responses are not understood, especially in lung fibroblasts. The authors investigated the role of ERK5 in bFGF induction of cell proliferation and in induction of PAI-1, a critical regulator of the pathological features of fibrosis, in lung fibroblasts. Main methods The role played by ERK5 in bFGF-induced PAI-1 expression was elucidated by perturbing the ERK5 signaling pathway using a specific chemical inhibitor and siRNA of ERK5. The effects of ERK5 signal perturbation on PAI-1 expression were measured at multiple levels by Q-PCR, immunoblotting, ELISA, and reporter gene analysis. The role of MEF2 in bFGF-induced activation of PAI-1 promoter activity via ERK5 was measured using a biotin-labeled DNA pull-down assay, and the effects of ERK5 on the mitogenic effects of bFGF were assessed using a MTT assay. Key findings In both primary human lung fibroblast and lung fibroblast cell lines, inhibition of ERK5 blocked bFGF-induced PAI-1 expression at both mRNA and protein levels and inhibited bFGF-induced PAI-1 promoter activity induction by bFGF. Upon stimulation with bFGF, MEF2 directly bound to the consensus sequence of the MEF2 binding site in the PAI-1 promoter. In addition, bFGF-induced PAI-1 up-regulation was inhibited by MEF2 siRNA, and bFGF-induced fibroblast proliferation was blocked by inhibiting ERK5. Significance This study reveals a novel role for the ERK5–MEF2 cascade, linking bFGF-induced PAI-1 expression and subsequent mitogenic processes in lung fibroblasts. more...
- Published
- 2014
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