Regression effect of hepatocyte nuclear factor 4α on liver cirrhosis in rats. Issue 6 (25th April 2013)

• Record Type: Journal Article
• Authors: Fan, Ting Ting; Hu, Ping Fang; Wang, Jian; Wei, Ji; Zhang, Qing; Ning, Bei Fang; Yin, Chuan; Zhang, Xin; Xie, Wei Fen; Chen, Yue Xiang; Shi, Bin
• Is Part Of: Journal of digestive diseases. Volume 14:Issue 6(2013:Jun.)
• Page Start: 318
• Page End: 327
• Publication Date: 2013-04-25
• Subjects: Digestive organs -- Diseases -- Periodicals; Gastroenterology -- Periodicals; 616.3
• DOI: 10.1111/1751-2980.12042
• Languages: English
• ISSNs: 1751-2972

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cdd12042-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="cdd12042-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="cdd12042-sec-0003" sec-type="section"> <title>Results</title> <p>Early stage of cirrhosis was remarkably resolved by HNF4α to a nearly‐normal extent and advanced cirrhosis was partially ameliorated <italic>in vivo</italic>. 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. <italic>In vivo</italic> and <italic>in vitro</italic> 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.</p> </sec> <sec id="cdd12042-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>