title: Regression effect of hepatocyte nuclear factor 4α on liver cirrhosis in rats.
abstract: OBJECTIVE
  The aim of this study was to determine whether cirrhosis could be reversed after treated with hepatocyte nuclear factor 4α (HNF4α), a key transcriptional regulator of hepatocyte differentiation and function.
  
  
  METHODS
  Early and advanced stages of liver cirrhosis were induced by thioacetamide (TAA) administration. The adenovirus carrying HNF4α gene was injected into cirrhotic rats via the tail vein. The effect of HNF4α on cirrhosis was evaluated by histological and immunohistochemical examination.
  
  
  RESULTS
  Early stage of cirrhosis was remarkably resolved by HNF4α to a nearly-normal extent and advanced cirrhosis was partially ameliorated in vivo. The enforced expression of HNF4α downregulated profibrogenic factors remarkably including α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, fibroblast-specific protein (FSP)-1, collagen I and III. In vivo and in vitro studies revealed that HNF4α administration inhibited extracellular signal-regulated kinase (ERK) signaling pathway through the downregulation of phosphorated ERK and phosphorated JunD. In addition, HNF4α readjusted the balance between extracellular matrix deposition and degradation through the upregulation of matrix metalloproteinase and downregulation of its inhibitors. Moreover, HNF4α treatment inhibited angiogenesis as determined by CD31 and CD34 immunostaining.
  
  
  CONCLUSIONS
  Our findings broaden the knowledge on the reversibility of different stages of cirrhosis as HNF4α could present a promising alternative for the treatment of liver cirrhosis.
authors: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors: Ting Ting
authors: TT
authors: Fan
authors: Ping Fang
authors: PF
authors: Hu
authors: Jian
authors: J
authors: Wang
authors: Ji
authors: J
authors: Wei
authors: Qing
authors: Q
authors: Zhang
authors: Bei Fang
authors: BF
authors: Ning
authors: Chuan
authors: C
authors: Yin
authors: Xin
authors: X
authors: Zhang
authors: Wei Fen
authors: WF
authors: Xie
authors: Yue Xiang
authors: YX
authors: Chen
authors: Bin
authors: B
authors: Shi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000627:therapeutic use*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide
chemical_list: D051557:Hepatocyte Nuclear Factor 4; D013853:Thioacetamide