2010 Fiscal Year Final Research Report

Role of macrophage scavenger receptor A in the progression of dietary steatohepatitis in mice

Research Project

Project/Area Number	21790682
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Gastroenterology
Research Institution	Osaka City University
Principal Investigator	FUJII Hideki Osaka City University, 大学院・医学研究科, 病院講師 (20382070)
Project Period (FY)	2009 – 2010
Keywords	肝臓 / 炎症 / 線維化 / メチオニン / コリン
Research Abstract	Male MSR-A knockout (MSR-A^<-/->) mice and age-matched C57Bl/6J (MSR-A^<+/+>) mice were fed either MCD diet or chow diet for 5 or 15 weeks. Inflammation and fibrosis were determined by tissue staining. Gene expressions were determined by quantitative reverse transcription-PCR (RT-PCR), respectively. MSR-A deficiency attenuated necroinflammatory reaction and macrophage accumulation, as indicated by histopathology and immunohistochemistry for F4/80, in mice fed the MCD diet. This condition reduced the hepatic expression of the proinflammatory genes, such as tumor necrosis factor-alpha, monocyte chemotactic protein 1, and macrophage colony stimulating factor and the profibrogenic genes, such as collagen type I alpha 1, collagen type III alpha 1,α-smooth muscle actin, tissue inhibitor of metalloproteinase-2, and connective tissue growth factor. In addition, MSR-A deficiency significantly reduced collagen deposition in the livers. These results indicate that MSR-A contributes to the augmentation of hepatic inflammation and fibrosis in the mouse model of steatohepatitis.