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

巨噬细胞清道夫受体A在小鼠饮食性脂肪性肝炎进展中的作用

• 批准号: 21790682
• 负责人: FUJII Hideki
• 金额: $ 2.83万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790682/
• 关键词: 肝臓; 炎症; 線維化; メチオニン; コリン; NASH; MSR-A

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.

雄性MSR-A敲除（MSR-A^<-/->）小鼠和年龄匹配的C57 Bl/6 J（MSR-A^<+/+>）小鼠饲喂MCD饲料或普通饲料5周或15周。通过组织染色确定炎症和纤维化。采用定量逆转录-PCR（RT-PCR）检测基因表达。如F4/80的组织病理学和免疫组织化学所示，在喂食MCD饲料的小鼠中，MSR-A缺乏减弱了坏死性炎症反应和巨噬细胞蓄积。这种情况降低了促炎基因（如肿瘤坏死因子-α、单核细胞趋化蛋白1和巨噬细胞集落刺激因子）和促纤维化基因（如I型胶原α 1、III型胶原α 1、α-平滑肌肌动蛋白、金属蛋白酶组织抑制剂-2和结缔组织生长因子）的肝脏表达。此外，MSR-A缺乏显著减少了肝脏中的胶原沉积。这些结果表明，MSR-A有助于脂肪性肝炎小鼠模型中肝脏炎症和纤维化的增强。

项目成果

Role of Macrophage Scavenger Receptor A in Hepatic Fibrogenesis of an Animal NASH Model

巨噬细胞清道夫受体 A 在动物 NASH 模型肝纤维形成中的作用

• 发表时间: 2010
• 作者: Yoshida N;Naito Y;Sakai K;et al.;Hideki Fujii
• 通讯作者: Hideki Fujii