The role of Gab1 adaptor protein during stem /progenitor cell-mediated liver regeneration in acute liver failure

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08997
• 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, 特任准教授 (40335352)
• Co-Investigator(Kenkyū-buntansha): 吉田 雄一 大阪大学, 医学系研究科, 特任助教 (30457014)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Gab1 / 重症肝不全 / 肝再生 / 幹細胞

Outline of Final Research Achievements

In this study, we assessed the role of Gab1 in stem/progenitor cell-mediated liver regeneration using chemically induced model. To induce the adult hepatic stem/progenitor cells, the wild type (WT) and hepatocyte specific Gab1 conditional knockout (CKO) mice were treated with 0.1% of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 2-6 weeks. Liver to body weight ratio of CKO mice was significantly lower than that of WT mice at 2, 4 and 6 week after DDC exposure. CKO mice also had a significant higher mortality compared to WT mice due to severe cholestasis. The induction of the CK19 positive adult hepatic stem/progenitor cells was reduced in CKO livers compared with WT livers. Consistently, the gene expression of hepatic stem cell markers, such as EpCAM and CD133/Prominin1 was significantly reduced in CKO livers compared with WT livers. These data showed that Gab1 might play a crucial role in stem/progenitor cell-mediated liver regeneration.

Free Research Field

肝再生