title: MeCP2 controls the expression of RASAL1 in the hepatic fibrosis in rats.
abstract: Hepatic stellate cells (HSCs) activation is an essential event during liver fibrogenesis. A major pathway is the transition of HSCs into hepatic myofibroblasts. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. Overexpression of this protein results in an increase of global methylation levels. Treatment of HSCs with DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC) blocks the cell proliferation. 5-azadC also prevents loss of Ras GTPase activating-like protein 1 (RASAL1) expression that occurs during HSCs proliferation. To further explore the underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis was caused by DNA methylation. Results demonstrated that hypermethylation of RASAL1 is associated with the perpetuation of fibroblast activation and fibrogenesis in the liver. knockdown of MeCP2 using siRNA technique increased RASAL1 in both mRNA and protein level in myofibroblasts. These studies demonstrated that MeCP2 and DNA methylation may provide molecular mechanisms for perpetuated fibroblast activation and fibrogenesis in the liver.
authors: School of pharmacy, Anhui key laboratory of bioactivity of natural products, Anhui Medical University, Hefei 230032, China.
authors: Hui
authors: H
authors: Tao
authors: Cheng
authors: C
authors: Huang
authors: Jing-Jing
authors: JJ
authors: Yang
authors: Tao-Tao
authors: TT
authors: Ma
authors: Er-Bao
authors: EB
authors: Bian
authors: Lei
authors: L
authors: Zhang
authors: Xiong-Wen
authors: XW
authors: Lv
authors: Yong
authors: Y
authors: Jin
authors: Jun
authors: J
authors: Li
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D000077209:Decitabine; D055785:Gene Knockdown Techniques; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins; D000077209:Decitabine; D001374:Azacitidine