A novel role of transforming growth factor beta1 in transcriptional repression of human cholesterol 7alpha-hydroxylase gene.

Title

A novel role of transforming growth factor beta1 in transcriptional repression of human cholesterol 7alpha-hydroxylase gene.

Creator

Li Tiangang; Chiang John Y L

Publisher

Gastroenterology

Date

2007
2007-11

Description

BACKGROUND & AIMS: Inhibition of cholesterol 7alpha-hydroxylase (CYP7A1) by bile acids and inflammatory cytokines provides an important mechanism to protect hepatocytes from bile acid toxicity during cholestasis. Transforming growth factor beta1 (TGFbeta1) released by hepatic stellate cells during chronic liver injury plays a critical role in liver inflammation and fibrogenesis. The objective of this study is to investigate the role of TGFbeta1 in hepatic bile acid synthesis. METHODS: mRNA expressions in primary human hepatocytes and HepG2 cells were measured by quantitative real-time polymerase chain reaction. Reporter assay, glutathione-S-transferase pull-down assay, adenovirus-mediated gene transduction, and chromatin immunoprecipitation assay were used to study the mechanism of TGFbeta1 regulation of CYP7A1 gene transcription. RESULTS: TGFbeta1 inhibited the mRNA expression of CYP7A1 and bile acid synthesis in HepG2 cells and primary human hepatocytes. Mothers against decapentaplegic homolog (Smad3) inhibited both CYP7A1 promoter activity and mRNA expression by inhibiting

Subject

Bile Acids and Salts/metabolism; Carcinoma; Cell Line; Cells; Cholesterol 7-alpha-Hydroxylase/*genetics/*metabolism; Cultured; Enzyme Inhibitors/pharmacology; Genetic/drug effects/*physiology; Hepatocellular/*metabolism/pathology; Hepatocyte Nuclear Factor 4/metabolism; Hepatocytes/drug effects/*metabolism/pathology; Humans; Hydroxamic Acids/pharmacology; Liver Neoplasms/*metabolism/pathology; Messenger/metabolism; RNA; Signal Transduction/physiology; Smad3 Protein/metabolism; Transcription; Transforming Growth Factor beta1/*metabolism; Tumor

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1660–1669

Issue

5

Volume

133

Citation

Li Tiangang; Chiang John Y L, “A novel role of transforming growth factor beta1 in transcriptional repression of human cholesterol 7alpha-hydroxylase gene.,” NEOMED Bibliography Database, accessed June 21, 2021, https://neomed.omeka.net/items/show/4029.

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