The role of heparin-binding EGF-like growth factor in liver fibrosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: KISO Shinichi 大阪大学, 医学(系)研究科(研究院), 特任准教授 (40335352)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Yuichi 大阪大学, 大学院医学系研究科, 助教 (30457014) ; WATABE Kenji 大阪大学, 医学部附属病院, 准教授 (50379244)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肝線維化 / 肝再生 / HB-EGF / 肝星細胞

Outline of Final Research Achievements

We reported that Heparin-binding EGF-like growth factor (HB-EGF) was a hepatotropic factor in vivo. However, the role of HB-EGF in liver fibrosis remains still unclear. Our aim is to evaluate the involvement of HB-EGF in liver fibrogenesis of mice. Gene expression of HB-EGF was increased in bile duct ligation (BDL)-induced fibrotic livers. We generated conditional HB-EGF knockout (KO) mice and were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis.

Free Research Field

消化器病学