Investigation of aggravating factors for renal fibrosis using kidney organoids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Koichiro Susa 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50735842)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腎臓オルガノイド / 修飾遺伝子 / 慢性腎臓病 / 線維化

Outline of Final Research Achievements

In chronic kidney disease (CKD), fibrosis progresses regardless of the primary disease. Therefore, renal fibrosis should be a promissing therapeutic target. Since the severity of renal fibrosis absolutely varies betweeen individuals, we hypothesize that there are aggravating factors that determine the severity. This study aims to identify these factors.
To this end, we have constructed a screening system including fluorescent reporter organoids to visualize fibrotic areas, and NPHP1-deficient iPS cells and organoids as a "fibrosis-prone kidney organoid model."
Furthermore, we compared protein and gene expression in wild-type and complete NPHP1 deficiency cases through comprehensive analysis. As a result, we identified several candidate proteins and genes that interact with NPHP1 and might contribute to fibrosis.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

上記のNPHP1欠損iPS細胞については、両アリルにおける長大な遺伝子欠失をiPS細胞において生じさせるその作製手法自体に新規性があったため、その部分について論文報告を行った。
また、本研究によってNPHP1と腎臓線維化を結び付ける因子も複数絞り込むことができ、NPHP1が関連する腎臓線維化の一部機序を解明する糸口をつかんだ。
今後、そこから腎臓線維化を増悪させる因子を同定し、最終的には国民病とも言えるCKDの治療法開発に貢献することを目指している。