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KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7 [KFL10 overexpression]

ABSTRACT: KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7 [KFL10 overexpression]

PROVIDER: PRJNA808617 | ENA |

REPOSITORIES: ENA

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KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7 [KFL10 overexpression]

Project description:Nonalcoholic steatohepatitis (NASH), characterized by hepatic steatosis, inflammation, and liver injury, has become a leading cause of end-stage liver diseases and liver transplantation. Krüppel-like factors 10 (KLF10) is a Cys2/His2 zinc finger transcription factor that regulates cell growth, apoptosis, and differentiation. However, whether it plays a role in the development and progression of chronic liver diseases like NASH remains poorly understood. In the present study, we found that KLF10 expression was selectively upregulated in the mouse models and human patients with NASH, compared with simple steatosis (NAFL). Gain- and loss-of function studies demonstrated that hepatocyte-specific overexpression of KLF10 aggravated, whereas its depletion alleviated diet-induced NASH pathogenesis in mice. Mechanistically, transcriptomic analysis and subsequent functional experiments showed that KLF10 promotes hepatic lipid accumulation and inflammation through the palmitoylation and plasma membrane localization of fatty acid translocase CD36 via transcriptionally activation of zDHHC7. Indeed, both expression of zDHHC7 and palmitoylation of CD36 are required for the pathogenic roles of KLF10 in NASH progression. Thus, our results identify an important role for KLF10 in NAFL-to-NASH development through zDHHC7-mediated CD36 palmitoylation.

2022-02-25 | GSE197054 | GEO

KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7 [NAFL vs NASH]

2022-02-25 | GSE197053 | GEO

KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7

Project description:KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7

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KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7 [NAFL vs NASH]

Project description:KLF10 promotes nonalcoholic steatohepatitis progression through transcriptional activation of zDHHC7 [NAFL vs NASH]

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AGXT overexpression during nonalcoholic steatohepatitis in mice

Project description:To investigate the effects of AAV8-mediated overexpression of AGXT in mice with diet-induced nonalcoholic steatohepatitis compared to AAV8-GFP

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Sparcl1 promotes nonalcoholic steatohepatitis progression through upregulation of CCL2

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Nonalcoholic steatohepatitis in adolescents undergoing bariatric surgery

Project description:The genomic landscape of hepatic tissue affected by nonalcoholic steatohepatitis (NASH) in severely obese adolescents undergoing bariatric surgery is unknown. Our purpose here was to uncover genomic profiles of obese controls, and obese cases with nonalcoholic fatty liver disease (NAFLD), borderline nonalcoholic steatohepatitis, and definite nonalcoholic steatohepatitis, in order to clarify molecular functions, biological processes, and pathways that are dysregulated in nonalcoholic steatohepatitis in the severely obese adolescent. In a prospective observational cohort study, we have intra-operatively obtained 165 liver samples; of these 67 were submited for microarray analysis. Through ANOVA, we found 8648 genes with differential regulation between the four histologies; from these, we uncovered gene signatures shared between borderline and definite nonalcoholic steatohepatitis, and gene sets with differential effects between borderline and definite.

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Nonalcoholic fatty liver, but not nonalcoholic steatohepatitis is a protective factor to tetrachloroethylene-associated kidney effects in male C57BL/6J mice

Project description:Purpose: We investigated the tetrachloroethylene associated changes in kidney transcriptomes among healthy mice, nonalcoholic fatty liver disease mice, and nonalcoholic steatohepatitis mice.

2019-02-13 | GSE115641 | GEO

Nonalcoholic fatty liver, but not nonalcoholic steatohepatitis is a protective factor to tetrachloroethylene-associated kidney effects in male C57BL/6J mice

2019-02-13 | GSE115641 | GEO

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