Investigation of Immunological Mechanisms of Renal Fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17273
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Gunma University
• Principal Investigator: Watanabe Mitsuharu 群馬大学, 医学部附属病院, 助教 (40865052)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腎線維化 / マクロファージ / Shp1

Outline of Final Research Achievements

Immune cells such as macrophages (MΦ) are thought to be involved in developing renal fibrosis, but the details are unclear. Therefore, we analyzed the kidneys of Shp1 CKO mice, which spontaneously develop renal fibrosis, by flow cytometry. We found that F4/80 high MΦs were significantly increased in the fibrotic kidneys of Shp1 CKO mice, and these MΦs expressed high levels of the fibrosis marker Vimentin and had high proliferative potential. Furthermore, renal F4/80 high MΦs with Shp1 CKO lacked Shp1 and showed enhanced M-CSF signaling. These results suggest that Shp1 negatively regulates M-CSF signaling in renal F4/80 high MΦs and suppresses renal fibrosis.

Free Research Field

免疫学、腎臓病学

Academic Significance and Societal Importance of the Research Achievements

Shp1は腎F4/80 high MΦのM-CSFシグナルを負に制御し、腎の線維化を抑制する可能性が示された。これらの事実は、F4/80 high MΦ、Shp1、M-CSFといった分子・細胞が腎線維化におけるkey playerである可能性を示している。腎線維化の免疫学的メカニズム解明のため重要な知見であると考えられ、さらには、これらをターゲットにした腎線維化における新規治療法の開発につながる可能性を示したと思われる。