Mechanistic insights into the effects of SREBP1c on hepatic stellate cell and liver fibrosis.

Journal of Cellular and Molecular Medicine
Shengyan SuYajun Zhou

Abstract

Sterol regulatory element-binding protein 1c (SREBP1c) plays key roles in maintenance of hepatic stellate cell (HSC) quiescence. The present researches investigated the mechanisms underlying the effects of SREBP1c on HSCs and liver fibrogenesis by HSC-targeted overexpression of the active SREBP1c using adenovirus in vitro and in vivo. Results demonstrated that SREBP1c exerted inhibitory effects on TAA-induced liver fibrosis. SREBP1c down-regulated TGFβ1 level in liver, reduced the receptors for TGFβ1 and PDGFβ, and interrupted the signalling pathways of Smad3 and Akt1/2/3 but not ERK1/2 in HSCs. SREBP1c also led to the decreases in the protein levels of the bromodomain-containing chromatin-modifying factor bromodomain protein 4, methionine adenosyltransferase 2B (MAT2B) and TIMP1 in HSCs. In vivo activated HSCs did not express cyclin D1 and cyclin E1 but SREBP1c down-regulated both cyclins in vitro. SREBP1c elevated PPARγ and MMP1 protein levels in the model of liver fibrosis. The effect of SREBP1c on MAT2B expression was associated with its binding to MAT2B1 promoter. Taken together, the mechanisms underlying the effects of SREBP1c on HSC activation and liver fibrosis were involved in its influences on TGFβ1 level, the recepto...Continue Reading

References

Nov 18, 1994·Cell·C J Sherr
Sep 2, 2000·The Journal of Biological Chemistry·T MiyaharaH Tsukamoto
Jun 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hajime HondaNobuhiro Sato
Nov 13, 2004·The Journal of Biological Chemistry·Hongyun SheHidekazu Tsukamoto
Feb 4, 2005·The Journal of Clinical Investigation·Ramón Bataller, David A Brenner
Dec 14, 2005·Alcoholism, Clinical and Experimental Research·Hide Tsukamoto
Feb 3, 2006·The Keio Journal of Medicine·Hide Tsukamoto
Jun 27, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Liu YangDon C Rockey
Apr 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·José M Mato, Shelly C Lu
Oct 1, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gakuhei SonRichard A Rippe
Jan 1, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Komal RamaniShelly C Lu
Mar 17, 2010·Molecular and Cellular Endocrinology·Yajun ZhouXiaoliang Sun
Apr 19, 2011·Best Practice & Research. Clinical Gastroenterology·Ursula E Lee, Scott L Friedman
Mar 29, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yulia A NevzorovaChristian Liedtke
Dec 9, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ning DingRonald M Evans
Oct 19, 2016·Journal of Hepatology·Fernando MagdalenoNatalia Nieto
Jul 20, 2017·F1000Research·Matthew S StrattonTimothy A McKinsey
Oct 21, 2017·Molecular Immunology·Xuguang ZhaiYajun Zhou

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Methods Mentioned

BETA
Assay
transfection
electrophoresis
immunoprecipitation
Chip
PCR

Software Mentioned

BioBase
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