A study of regulation of Kupffer-cell activation by intracellular lipid metabolism and its involvement in the pathogenesis of liver fibrosis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16103
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Tohoku University
• Principal Investigator: MIYAZAKI Hirofumi 東北大学, 医学系研究科, 助教 (90803867)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マクロファージ / 肝線維化 / 脂肪酸結合蛋白質

Outline of Final Research Achievements

Liver macrophages (Kupffer cells, KCs) activate their functions upon changes in the liver environment and play important roles in pathological conditions such as nonalcoholic steatohepatitis and liver fibrosis, but the molecular basis of KC activation is still unclear. In this study, we focused on FABP7, a molecule specifically expressed in KC, and investigated the regulatory mechanism of KC activation in liver disease models. The results showed that FABP7 in KC promotes liver fibrosis. On the other hand, it was also shown that FABP7 may be less involved in hepatic lipid accumulation and hepatic tissue inflammation. Furthermore, FABP7 may regulate the activation of anti-inflammatory functions of KC and promote fibrotic responses of fibroblasts. In the future, we would like to elucidate the regulatory molecular mechanism of KC activation by FABP7 in more detail.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、KC特異的に発現する分子FABP7がKCの抗炎症性機能制御機構を介して、肝線維化促進に作用することを示した。肝線維化は肝臓の炎症治癒の役割を果たす一方、肝硬変や肝細胞癌への誘引リスクでもある。FABP7はリガンドである長鎖脂肪酸の細胞内生理機能を制御すると考えられ、今後、長鎖脂肪酸やFABP7によるKCの活性化制御機構をより詳細に明らかにすることにより、KC機能が関与する肝疾患の予防や治療法の開発が期待できる。