Approaches to the pathogenesis and treatment of liver fibrosis through genetically modified mice.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Mie University
• Principal Investigator: IWASA Motoo 三重大学, 医学(系)研究科(研究院), 准教授 (80378299)
• Co-Investigator(Kenkyū-buntansha): GABAZZA Esteban 三重大学, 医学系研究科, 教授 (00293770)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: アルコール性肝障害

Outline of Final Research Achievements

This study investigated the role of protein S in acute alcoholic hepatitis. A mouse overexpressing human protein S (hPS-TG) was generated in which acute hepatitis was induced by intraperitoneal injection of ethanol. The levels of serum liver enzymes, liver tissue inflammatory cytokines and the degree of hepatic steatosis were significantly increased in hPS-TG mice treated with ethanol. Cell expansion, activation and inhibition of apoptosis were significantly augmented in natural killer T (NKT) cells from hPS-TG mice. In a co-culture system of hepatocytes and NKT cells, the effects of protein S on ethanol-mediated cell injury were suppressed by a CD1d neutralizing antibody. NKT cells from patients with alcoholic hepatitis had increased levels of protein S and CD1d mRNA. Protein S exacerbates acute alcoholic hepatitis by enhancing the activation of NKT cells, indicating that protein S may be a molecular target for therapy of this disease.

Free Research Field

肝臓病学