Elucidation of unique characteristics of renal fibroblasts in fibrosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19550
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kurashima Yosuke 東京大学, 医科学研究所, 特任准教授 (30729372)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 線維化 / 線維芽細胞 / マスト細胞 / コラーゲン / マクロファージ / 慢性炎症

Outline of Final Research Achievements

Excessive accumulation of extracellular matrix such as type I collagen induced fibrosis and eventually causing organ failure. In kidney, renal interstitial fibrosis is a common pathology when chronic kidney disease was aggravated. However, the underlined mechanisms of kidney fibrosis especially interstitial fibrosis have not been well elucidated. We newly found unique myeroid cell populations, which are capable of producing collagen, are increased in the fibrotic kidney. Those myeroid cell populations are induced by fibrogenic renal fibroblasts in vitro. Importantly, those fibrogenic fibroblasts are increased by activation of mast cells. Taken together, the triangular interaction of those cellular populations could be a major pathological event for renal fibrotic disease and considered as a new drug target.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本課題はこれまで申請者が取り組んできた、生体恒常性維持のための「線維芽細胞―免疫細胞相互作用」についての研究成果から着想を進めた研究課題である。本研究から、コラーゲンを選択的に産生し、線維化促進に働くミエロイド系細胞を見出し、この細胞の誘導プロセスから腎線維芽細胞の特殊性や新たな活性化機序が明らかになった新規性・独自性の高い研究として位置付けられる。
「組織特異的な病原性線維芽細胞による線維化誘導機構」という新しいコンセプトの立証に繋がると考えられ、病原性線維芽細胞を標的とした新規治療につながる成果である。