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Background: Ubiquitin-specific protease 7 (USP7) has been found to be associated with motor function recovery after spinal cord injury (SCI). Therefore, its role and mechanism in SCI process need further exploration. Methods: SCI rat models were established via performing laminectomy at the T9-T11 spinal vertebrae and cutting spinal cord tissues. SCI cell models were constructed by inducing PC12 cells with lipopolysaccharide (LPS). The protein levels of USP7, nuclear respiratory factor 1 (NRF1), Krüppel-like factor 7 (KLF7) and apoptosis-related markers were detected by western blot. Cell viability and apoptosis were tested by cell counting kit-8 assay and flow cytometry. The contents of inflammatory factors were examined using ELISA. The interaction between NRF1 and USP7 or KLF7 was analyzed by co-immunoprecipitation assay, chromatin immunoprecipitation assay and dual-luciferase reporter assay, respectively. Results: USP7 was downregulated in SCI rat models and LPS-induced PC12 cells. Overexpressed USP7 promoted viability, while repressed apoptosis and inflammation in LPS-induced PC12 cells. USP7 could stabilize NRF1 protein expression via deubiquitination, and NRF1 knockdown reversed the protective effect of USP7 against LPS-induced PC12 cell injury. NRF1 is bound to KLF7 promoter to enhance its transcription. NRF1 overexpression inhibited LPS-induced PC12 cell inflammation and apoptosis via increasing KLF7 expression. Conclusion: USP7 alleviated inflammation and apoptosis in LPS-induced PC12 cells via NRF1/KLF7 axis, indicating that targeting of USP7/NRF1/KLF7 axis might be a promising treatment strategy for SCI. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a condition characterized by inflammation and excessive collagen deposition, which has been identified as a potentially malignant disorder. Recently, several microRNAs (miRNAs) have been shown to be implicated in various disorders associated with fibrosis. However, how these miRNAs modulate OSF development is poorly understood. Therefore, the study aimed to identify the specific miRNAs that contribute to the progression of OSF and to investigate their molecular mechanisms in promoting fibrosis. The expression and clinical significance of potential pro-fibrosis miRNA in the OSF cohort and primary buccal mucosal fibroblasts were confirmed through RNA sequencing and qRT–PCR. Luciferase reporter activity assay, miRNA mimic or inhibitor, and short-hairpin RNA silencing were used to elucidate the molecular mechanism of miRNA. Transwell migration, collagen contraction, and reactive oxygen species (ROS) generation detection were used to investigate the effects of this mechanism on the myofibroblast phenotype and cellular pro-fibrosis capacity. This study demonstrated that miR-190a was overexpressed in fibrotic buccal mucosal fibroblasts (fBMFs). Transfecting fBMFs with miR-190a inhibitor resulted in reduced cell migration, collagen gel contraction, ROS generation, and expression of fibrotic markers. Furthermore, miR-190a exerted this pro-fibrosis property by direct binding to its target, Krüppel-like factor 15 (KLF15). The results also indicated that the aberrant upregulation of miR-190a, in turn, downregulated the expression of KLF15, which resulted in the activation of myofibroblast. Our findings demonstrated that miR-190a was involved in myofibroblast activation, suggesting that targeting the miR-190a/KLF15 axis may be a feasible approach in the therapy of OSF. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a chronic nasal inflammation, characterized by nasal epithelial dysfunction. Gene therapy targeting transcription factors is a promising strategy for quenching allergic inflammation, including AR. Objective: This study sought to probe the mechanism of Kruppel-like factor 4 (KLF4) in pyroptosis of nasal mucosal epithelial cells (NEpCs) in AR mice and provide targets for AR treatment. Methods: AR mouse models were established using sensitization with ovalbumin, followed by injection with short hairpin RNA KLF4 (sh-KLF4). AR symptoms were assessed by the times of sneezing and nose rubbing, hematoxylin-eosin, and periodic acid-Schiff staining. Levels of KLF4, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, and N-terminal domain (GSDMD-N) in nasal mucosal tissues were determined by Western blot assay, and levels of interleukin (IL)-1β and IL-18 in nasal lavage fluid were determined by enzyme-linked immunosorbent assay. The binding of KLF4 to the NLRP3 promoter was verified using chromatin immunoprecipitation and dual-luciferase assays. The functional rescue experiment was performed with oe-NLRP3 and sh-KLF4 in AR mice. Results: KLF4 was upregulated in nasal mucosal tissues of AR mice. KLF4 inhibition reduced the times of sneezing and nose rubbing, inflammatory cell infiltration, and goblet cell hyperplasia in nasal mucosal tissues, and levels of NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, and IL-18. KLF4 was enriched on the NLRP3 promoter and improved NLRP3 expression. NLRP3 overexpression reversed the inhibition of sh-KLF4 on pyroptosis of NEpCs in AR mice. Conclusion: KLF4 bound to the NLRP3 promoter and promoted pyroptosis of NEpCs in AR mice via activating NLRP3. [ABSTRACT FROM AUTHOR]

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Krüppel-like factor 15 (KLF15) has been reported to be involved in ischemia injury of multiple types of diseases. Nevertheless, the roles and underlying mechanisms of KLF15 in preeclampsia (PE) are still unclear. In this study, the expression of KLF15 in placenta tissues and hypoxia/reoxygenation (H/R)-induced HTR8/SVneo cells was evaluated by GSE66273 database, qRT-PCR and western blot assay. CCK-8 assay was employed to detect cell proliferation. Wound healing assay and transwell assay were used to detect cell migration and invasion. Cell oxidative stress was measured by DCFH-DA staining and kits. Cell apoptosis was evaluated by TUNEL assay and western blot assay. The JASPAR database was used to analyze the binding site of KLF15 and insulin-like growth factor-1 receptor (IGF1R) promoter region. The luciferase reporter assay was used to detect IGF1R promoter activity and ChIP assay was used to verify the combination of KLF15 and IGF1R promoter. Moreover, western blot was employed to measure the expressions of PI3K/Akt-related proteins. The data showed that the expression of KLF15 was significantly downregulated in GSE66273 database, tissues and HTR8/SVneo cells. KLF15 overexpression increased H/R-induced HTR8/SVneo cell proliferation, invasion and migration, and inhibited oxidative stress and cell apoptosis. In addition, IGF1R was highly expressed in H/R-induced HTR8/SVneo cells after KLF15 overexpression, and the binding of KLF15 and IGF1R promoter was verified. Silencing of IGF1R reversed the effects of KLF15 overexpression on H/R-induced HTR8/SVneo cell proliferation, migration, invasion, oxidative stress and cell apoptosis. Moreover, KLF15 overexpression and IGF1R silencing regulated the expressions of PI3K/Akt-related proteins in H/R-induced HTR8/SVneo cells. In conclusion, KLF15 overexpression promoted the proliferation and metastasis, and suppressed oxidative stress and cell apoptosis of H/R-induced HTR8/SVneo cells through mediating the PI3K/Akt pathway, which may provide a promising target for the treatment of preeclampsia. • KLF15 overexpression improves H/R-induced proliferation, invasion and migration in HTR8/SVneo cells. • KLF15 overexpression ameliorates oxidative stress and apoptosis induced by H/R treatment. • KLF15 regulates PI3K/Akt signaling to affect H/R-induced trophoblast cells through transcriptional activation of IGF1R. [ABSTRACT FROM AUTHOR]

Exercise is an effective non-pharmacological strategy for the treatment of nonalcoholic steatohepatitis (NASH), but the underlying mechanism needs further investigation. Kruppel-like factor 10 (Klf10) is a transcriptional factor that is expressed in multiple tissues including liver, whose role in NASH is not well defined. In our study, exercise induces hepatic Klf10 expression through the cAMP/PKA/CREB pathway. Hepatocyte-specific knockout of Klf10 (Klf10LKO) increases lipid accumulation, cell death, inflammation and fibrosis in NASH diet-fed mice and reduces the protective effects of treadmill exercise against NASH, while hepatocyte-specific overexpression of Klf10 (Klf10LTG) works in concert with exercise to reduce NASH in mice. Mechanistically, Klf10 promotes the expression of fumarate hydratase 1 (Fh1), thereby reducing fumarate accumulation in hepatocytes. This decreases the trimethyl (me3) levels of histone 3 lysine 4 (H3K4me3) on lipogenic genes promoters to attenuate lipogenesis, thus ameliorating free fatty acids (FFAs)-induced hepatocytes steatosis, apoptosis, insulin resistance and blunting dysfunctional hepatocytes-mediated activation of macrophages and hepatic stellate cells. Therefore, by regulating the Fh1/fumarate/H3K4me3 pathway, Klf10 acts as a downstream effector of exercise to combat NASH. [Display omitted] • Exercise induces hepatic Klf10 expression in mice through the cAMP/PKA/CREB pathway. • Hepatic Klf10 deficiency undermines exercise-mediated alleviation of NASH. • Overexpression of hepatic Klf10 relieves NASH in synergy with exercise. • Hepatic Klf10 confers the protective effects of exercise against NASH by inhibiting lipogenesis via Klf10/Fh1 axis. [ABSTRACT FROM AUTHOR]

Krüppel-like factor 10 (KLF10), a zinc finger transcription factor, plays a pivotal role in modulating TGF-β-mediated cellular processes such as growth, apoptosis, and differentiation. Recent studies have implicated KLF10 in regulating lipid metabolism and glucose homeostasis. This study aimed to elucidate the precise role of hepatic KLF10 in developing metabolic dysfunction-associated steatohepatitis (MASH) in diet-induced obese mice. We investigated hepatic KLF10 expression under metabolic stress and the effects of overexpression or ablation of hepatic KLF10 on MASH development and lipidemia. We also determined whether hepatocyte nuclear factor 4α (HNF4α) mediated the metabolic effects of KLF10. Hepatic KLF10 was downregulated in MASH patients and genetically or diet-induced obese mice. AAV8-mediated overexpression of KLF10 in hepatocytes prevented Western diet-induced hypercholesterolemia and steatohepatitis, whereas inactivation of hepatocyte KLF10 aggravated Western diet-induced steatohepatitis. Mechanistically, KLF10 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis, and reducing hepatic cholesterol levels by promoting bile acid synthesis. KLF10 highly induced HNF4α expression by directly binding to its promoter. The beneficial effect of KLF10 on MASH development was abolished in mice lacking hepatocyte HNF4α. In addition, the inactivation of KLF10 in hepatic stellate cells exacerbated Western diet-induced liver fibrosis by activating the TGF-β/SMAD2/3 pathway. Our data collectively suggest that the transcription factor KLF10 plays a hepatoprotective role in MASH development by inducing HNF4α. Targeting hepatic KLF10 may offer a promising strategy for treating MASH. • Hepatic KLF10 is markedly reduced in MASLD patients and Western diet-induced or genetically obese mice. • Hepatocyte KLF10 is required and sufficient to protect against Western diet-induced steatohepatitis and hypercholesterolemia. • Hepatocyte KLF10 protects against MASH via induction of HNF4α. • HNF4α is a direct target gene of KLF10. • Ablation of KLF10 in stellate cells promotes fibrogenesis by activating SMAD2/3. [ABSTRACT FROM AUTHOR]

We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel‐like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe−/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe−/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis. Oil red O-stained sections of atherosclerotic lesion area in the aortic root [ABSTRACT FROM AUTHOR]

Skeletal muscle is a hierarchical structure composed of multiple organizational scales. A major challenge in the biomechanical evaluation of muscle relates to the difficulty in evaluating the experimental mechanical properties at the different organizational levels of the same tissue. Indeed, the ability to integrate mechanical properties evaluated at various levels will allow for improved assessment of the entire tissue, leading to a better understanding of how changes at each level evolve over time and/or impact tissue function, especially in the case of muscle diseases. Therefore, the purpose of this study was to analyze a genetically engineered mouse model (Klf10 KO: Krüppel-Like Factor 10 knockout) with known skeletal muscle defects to compare the mechanical properties with wild-type (WT) controls at the three main muscle scales: the macroscopic (whole muscle), microscopic (fiber) and submicron (myofibril) levels. Passive mechanical tests (ramp, relaxation) were performed on two types of skeletal muscle (soleus and extensor digitorum longus (EDL)). Results of the present study revealed muscle-type specific behaviors in both genotypes only at the microscopic scale. Interestingly, loss of Klf10 expression resulted in increased passive properties in the soleus but decreased passive properties in the EDL compared to WT controls. At the submicron scale, no changes were observed between WT and Klf10 KO myofibrils for either muscle; these results demonstrate that the passive property differences observed at the microscopic scale (fiber) are not caused by sarcomere intrinsic alterations but instead must originate outside the sarcomeres, likely in the collagen-based extracellular matrix. The macroscopic scale revealed similar passive mechanical properties between WT and Klf10 KO hindlimb muscles. The present study has allowed for a better understanding of the role of Klf10 on the passive mechanical properties of skeletal muscle and has provided reference data to the literature which could be used by the community for muscle multiscale modeling. [Display omitted] • Role of Klf10 on the passive behavior of muscle at three organizational scales. • Klf10 impacts differentially the passive properties of the soleus and EDL muscles. • Lack of Klf10 expression does not change the passive behavior of myofibrils. • Disruption of Klf10 on skeletal muscle is primarily at the microscopic scale. [ABSTRACT FROM AUTHOR]

The incidence of pulmonary fibrosis is on the rise, and existing treatments have limited efficacy in improving patient survival. The purpose of this study was to reveal the potential of Krüppel-like factor (KLF)15 activation in alleviating pulmonary fibrosis. Transforming growth factor beta (TGF-β) was utilized to induce lung fibroblasts to establish an in vitro model of pulmonary fibrosis. The impacts of TGF-β and KLF15 level on cell proliferation, migration, extracellular matrix (ECM) accumulation, and endoplasmic reticulum stress (ERS) were assessed. Additionally, tunicamycin, an ERS agonist, was used to investigate the role of ERS in KLF15 regulation. The results showed that KLF15 was dropped in response to TGF-β treatment. However, KLF15 overexpression reduced cell proliferation, migration, ECM accumulation, and ERS, alleviating the effects of TGF-β stimulation. Subsequent treatment with tunicamycin diminished the effects of KLF15 overexpression, demonstrating that ERS mediated the modulation of KLF15. KLF15 acts against ERS and suppresses excessive proliferation and ECM accumulation in lung fibroblast. These findings suggest that activating KLF15 is a promising strategy for alleviating pulmonary fibrosis. • TGF-β1 induces a decrease in KLF15 in MRC-5 cells. • KLF15 regulates cell proliferation, migration, and extracellular matrix accumulation. • KLF15 is involved in ERS. [ABSTRACT FROM AUTHOR]

We aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats. Pregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system. High iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = −0.909, p = 0.012; r = −0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = −0.917, p = 0.01; r = −0.859, p = 0.028; r = −0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = −0.990, p = 0.0002) and Txnrd2 expression (r = −0.979, p = 0.001; r = −0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased. In addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function. [Display omitted] • In both maternal and offspring rats, high iodide intake during pregnancy and lactation results in increased UIC, STIC, SNBIC, FT3 and its target gene KLF9. • In high iodide intake maternal rats, alteration of STIC, SNBIC, KLF9, Txnrd2 and EET metabolites contribute to the increased SBP and cardiac hyperfunction. • In offspring rats, much lower STIC, SNBIC and higher EPAs may contribute to the normal cardiovascular function. • TH, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide-induced thyroid and cardiovascular function. [ABSTRACT FROM AUTHOR]

Recent developments in the analysis of epigenetic DNA methylation patterns have demonstrated that certain genetic loci show a linear correlation with chronological age. It is the goal of this study to identify a new set of epigenetic methylation markers for the forensic estimation of human age. A total number of 27 CpG sites at three genetic loci, SCGN , DLX5 and KLF14 , were examined to evaluate the correlation of their methylation status with age. These sites were evaluated using 72 blood samples and 91 saliva samples collected from volunteers with ages ranging from 5 to 73 years. DNA was bisulfite modified followed by PCR amplification and pyrosequencing to determine the level of DNA methylation at each CpG site. In this study, certain CpG sites in SCGN and KLF14 loci showed methylation levels that were correlated with chronological age, however, the tested CpG sites in DLX5 did not show a correlation with age. Using a 52-saliva sample training set, two age-predictor models were developed by means of a multivariate linear regression analysis for age prediction. The two models performed similarly with a single-locus model explaining 85% of the age variance at a mean absolute deviation of 5.8 years and a dual-locus model explaining 84% of the age variance with a mean absolute deviation of 6.2 years. In the validation set, the mean absolute deviation was measured to be 8.0 years and 7.1 years for the single- and dual-locus model, respectively. Another age predictor model was also developed using a 40-blood sample training set that accounted for 71% of the age variance. This model gave a mean absolute deviation of 6.6 years for the training set and 10.3 years for the validation set. The results indicate that specific CpGs in SCGN and KLF14 can be used as potential epigenetic markers to estimate age using saliva and blood specimens. These epigenetic markers could provide important information in cases where the determination of a suspect’s age is critical in developing investigative leads. [ABSTRACT FROM AUTHOR]

Rabbit induced pluripotent stem cells (rbiPSCs) possess the characteristic features of primed pluripotency as defined in rodents and primates. In the present study, we reprogrammed rbiPSCs using human Krüppel-like factors (KLFs) 2 and 4 and cultured them in a medium supplemented with fetal calf serum and leukemia inhibitory factor. These cells (designated rbEKA) were propagated by enzymatic dissociation for at least 30 passages, during which they maintained a normal karyotype. This new culturing protocol resulted in transcriptional and epigenetic reconfiguration, as substantiated by the expression of transcription factors and the presence of histone modifications associated with naïve pluripotency. Furthermore, microarray analysis of rbiPSCs, rbEKA cells, rabbit ICM cells, and rabbit epiblast showed that the global gene expression profile of the reprogrammed rbiPSCs was more similar to that of rabbit ICM and epiblast cells. Injection of rbEKA cells into 8-cell stage rabbit embryos resulted in extensive colonization of ICM in 9% early-blastocysts (E3.5), epiblast in 10% mid-blastocysts (E4.5), and embryonic disk in 1.4% pre-gastrulae (E6). Thus, these results indicate that KLF2 and KLF4 triggered the conversion of rbiPSCs into epiblast-like, embryo colonization-competent PSCs. Our results highlight some of the requirements to achieve bona fide chimeric competency. [ABSTRACT FROM AUTHOR]

This study is to investigate the effect of Kruppel-like factor 9 (KLF9) on the occurrence and progression of cholangiocarcinoma (CCA) and its underlying mechanism. After the CCA cells were transfected with OE-KLF9 and/or sh-metallothionein 1 M (sh-MT1M), KLF9 and MT1M expression levels were measured. Likewise, the biological characteristics of CCA cells were measured, followed by detections of caspase3 activity and epithelial mesenchymal transition (EMT)-related protein. Furthermore, the binding site of KLF9 and MT1M was predicted and verified. An in vivo model of CCA in nude mice was established where tumor volume and weight were recorded, in addition to tumor metastasis in the liver. The expression of KLF9 and MT1M in the CCA cells was remarkably lower. CCA cells overexpressing KLF9 showed repressed abilities to proliferate, invade, and migrate, and strengthened cell apoptosis. KLF9 inhibited EMT, growth, and migration of CCA cells by modulating MT1M transcription. Additionally, KLF9 facilitated MT1M expression in vivo and improve the progression of CCA in nude mice. KLF9 acted as a transcription factor of MT1M to promote its transcription level, thereby affecting the growth and migration of CCA cells, and ultimately improving the occurrence and development of CCA. • KLF9 suppresses the migration of CCA cells. • KLF9 modulates the transcription of MT1M in a targeted fashion. • KLF9 inhibits growth and migration of CCA cells by regulating MT1M transcription. • KLF9 modulates MT1M transcription and restrains development of CCA in vivo. [ABSTRACT FROM AUTHOR]

Krüppel-like factor 4 (KLF4) functions as either a tumor suppressor or an oncogene in different tissues by regulating the expression of various genes. The aim of this study was to reveal the functions of KLF4 in regulating breast cancer apoptosis, proliferation, and tumorigenic progression. KLF4 expression levels in breast cancer tissues and breast cancer cell lines were found to be much lower than those in nontumorous tissues and a nontransformed mammary epithelial cell line. KLF4 was upregulated in the tumor necrosis factor-α–induced SK-BR-3 breast cancer cell apoptotic process. Overexpression of KLF4 promoted SK-BR-3 breast cancer cell apoptosis and suppressed SK-BR-3 cell tumorigenicity in vivo . [ABSTRACT FROM AUTHOR]

The article studies the functional analysis of Krüppel-like factor 3 (KLF3) in adipose tissue of chicken. It informs that during the study, the expression of chicken KLF3 was observed during the growth and development of abdominal fat tissue. In further study, over-expression of gallus gallus KLF3 (gKLF3) was found to suppress CCAAT/ enhancer binding protein alpha (C/EBPa).

Background & Aims: Krüppel-like factor 4 (Klf4) is a putative gastric tumor suppressor gene. Rare, villin-positive progenitor cells in the gastric antrum have multilineage potential. We investigated the function of Klf4 in these cells and in gastric carcinogenesis. Methods: We created mice with disruption of Klf4 in villin-positive antral mucosa cells (Villin-Cre + ;Klf4fl/fl mice). Villin-Cre + ;Klf4fl/fl and control mice were given drinking water with or without 240 ppm N-methyl-N-nitrosourea at 5 weeks of age and thereafter on alternating weeks for a total of 10 weeks. Gastric mucosa samples were collected at 35, 50, or 80 weeks of age from mice that were and were not given N-methyl-N-nitrosourea, and analyzed by histopathologic and molecular analyses. Findings were compared with those from human gastric tumor specimens. Results: Preneoplasia formed progressively in the antrum in 35- to 80-week-old Villin-Cre + ;Klf4fl/fl mice. Gastric tumors developed in 29% of 80-week-old Villin-Cre + ;Klf4fl/fl mice, which were located exclusively in the lesser curvature of the antrum. N-methyl-N-nitrosourea accelerated tumor formation, and tumors developed significantly more frequently in Villin-Cre + ;Klf4fl/fl mice than in control mice, at 35 and 50 weeks of age. Mouse and human gastric tumors had reduced expression of Krüppel-like factor 4 and increased expression of FoxM1 compared with healthy gastric tissue. Expression of Krüppel-like factor 4 suppressed transcription of FoxM1. Conclusions: Inactivation of Klf4 in villin-positive gastric progenitor cells induces transformation of the gastric mucosa and tumorigenesis in the antrum in mice. Villin-Cre + ;Klf4fl/fl have greater susceptibility to chemical-induced gastric carcinogenesis and increased rates of gastric tumor progression than control mice. [Copyright &y& Elsevier]

Background & Aims: Krüppel-like factor 4 (KLF4) is a transcription factor and putative tumor suppressor. However, little is known about its effects in hepatocellular carcinogenesis. We investigated the clinical significance, biologic effects, and mechanisms of dysregulated KLF4 signaling. Methods: We performed microarray analysis of hepatocellular carcinoma (HCC) tissues. We used molecular biology analyses and animal models to evaluate activation and function of KLF4-vitamin D receptor (VDR) pathway. Results: Expression of KLF4 protein was decreased or lost in primary HCC samples, in particular, lymph node metastases, compared with normal liver tissues. Loss of KLF4 from primary tumors was significantly associated with reduced survival time and was identified as a prognostic marker. Most human HCC cell lines had losses or substantial decreases in levels of KLF4. Exogenous expression of KLF4 in HCC cells upregulated expression of mesenchymal-epithelial transition (MET) and inhibited their migration, invasion, and proliferation in vitro. When these cells were injected into mice, tumors grew more slowly and metastatsis was inhibited, compared with HCC cells that did not express KLF4. VDR is a direct transcriptional target of KLF4; we identified 2 sites in the VDR promoter that bound specifically to KLF4. Increased expression of VDR sensitized tumor cells to the inhibitory effects of vitamin D. Conclusions: KLF4 binds to the promoter of VDR to regulate its expression; levels of KLF4 are reduced and levels of VDR are increased in HCC cell lines and primary tumor samples. Expression of KLF4 in HCC cells sensitizes them to the anti-proliferative effects of VD3. This pathway might be manipulated to prevent or treat liver cancer. [ABSTRACT FROM AUTHOR]