Development of the Treatment for Renal Fibrosis Mediated by Histone Modifications that Alter Macrophage Function

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16221
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Hiroshima University
• Principal Investigator: Sasaki Kensuke 広島大学, 病院(医), 助教 (40770326)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: マクロファージ / epigenetics / 免疫記憶 / SET7/9

Outline of Final Research Achievements

This study elucidates the involvement of the histone methyltransferase SET7/9 in renal fibrosis within macrophages (Mφ) and investigates the impact of SET7/9-mediated immune memory on renal fibrosis.
In the renal fibrosis model, the expression of SET7/9 translocates from tubular cells to interstitial cells over time, aligning with markers of immune cells, specifically Mφ. Furthermore, renal fibrosis was suppressed in SET7/9 knockout mice, generated using newly developed techniques, prompting further evaluation of polarity and phenotypic alterations in renal Mφ and bone marrow cells extracted from renal tissues. Additionally, the utilization of Mφ-specific SET7/9 knockout models will facilitate the exploration of the immunomodulatory effects conferred by SET7/9-mediated immune memory on renal fibrosis.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

近年、マクロファージ(Mφ)の環境や刺激による変化には、エピジェネティックな遺伝子制御が関与することが報告されており、本研究は、エピジェネティックなヒストンメチル化酵素SET7/9のもつ“免疫記憶”への変化が腎線維化にどのような影響を与えるのかを明らかにする。免疫細胞をターゲットとした治療法は免疫チェックポイント阻害薬やCAR-T細胞療法、CAR-M細胞療法など近年注目されてきており、本研究によりMφを用いた治療法が腎不全の分野でも臨床応用につながれば、新たな腎疾患治療薬となりうる。