Molecular mechanism of liver fibrosis progression by CCR2-positive macrophages in NASH

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K11791
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Okayama University
• Principal Investigator: Inagaki Junko 岡山大学, 医歯薬学域, 助教 (90271056)
• Co-Investigator(Kenkyū-buntansha): 渡辺 彰吾 岡山大学, 保健学域, 准教授 (20548341) ; 廣畑 聡 岡山大学, 保健学域, 教授 (90332791)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: NASH / CCR2陽性マクロファージ / 線維化 / オステオポンチン / マクロファージ

Outline of Final Research Achievements

We analyzed the expression regions of CCR2 and osteopontin (OPN) using NASH rat model liver tissues, to elucidate the molecular mechanism of liver fibrosis in nonalcoholic steatohepatitis (NASH). In this study, the OPN expression region expanded as the increased number of　weeks of HFC diet feeding, but its expression was observed only in the macrophages in the early stage of fibrosis. Moreover, as liver fibrosis progressed, OPN-positive region expanded and CCR2 was attenuated in the macrophage aggregation. Therefore, in the early stage of fibrosis, the macrophage aggregation was mainly composed CCR2-positive macrophages and gradually became OPN-positive macrophages. It became clear that a dynamic change of replacement occurs. This result suggests that there are different groups of OPN-positive and CCR2-positive macrophages and they may be closely related.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究成果より、肝線維化早期には、主にCCR2陽性マクロファージがマクロファージ集簇を構成し、次第にそれらがOPN陽性マクロファージに置き換わるという動態変化が起きる可能性を示すことができた。両マクロファージおよびOPNによる肝線維化促進の分子メカニズムを明らかにすることで、肝線維化治療の新たな創薬ターゲットの発見、治療法の開発および創薬研究につながると期待される。