Screening of humoral pathogenesis of idiopathic focal segmental glomerulosclerosis by proteinuria visualized transparent model animal

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K22618
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Nagoya University
• Principal Investigator: Maruyama Shoichi 名古屋大学, 医学系研究科, 教授 (10362253)
• Co-Investigator(Kenkyū-buntansha): 秋山 真一 名古屋大学, 医学系研究科, 特任講師 (20500010) ; 古橋 和拡 名古屋大学, 医学部附属病院, 病院講師 (50835121)
• Project Period (FY): 2019-06-28 – 2023-03-31
• Keywords: 巣状分節性糸球体硬化症 / 液性因子 / 巣状分節性糸球体硬化症

Outline of Final Research Achievements

Idiopathic focal segmental glomerulosclerosis (FSGS) is an extremely difficult-to-treat renal disease in which half of patients relapse within a few days after kidney transplantation. To understand the pathogenesis of FSGS, this study challenged the identification of the humoral etiologic agent responsible for FSGS, the molecule predicted to be present in patient blood based on previous findings. In this study, the in vivo assay using nephron-visible transparent zebrafish, which was invented by us, was used as the technical basis for the search for the humoral factors. As a result, although we could not identify the liquid factor within the study period, we found that a part of plasma from patients with FSGS and other renal diseases induced proteinuria in the said zebrafish, providing collateral evidence for the presence of the liquid factor in the patients' blood.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果の学術的意義は、糸球体バリア透過性亢進に係る未知の液性因子の探索に申請者らが発明した新規モデル動物であるネフロン可視化ゼブラフィッシュを用いたin vivoスクリーニングシステムが有用であることのフィジビリティを確立できた点、ならびに、FSGSや他腎疾患の患者血液にゼブラフィッシュの糸球体バリア透過性を亢進させる液性因子が存在することの傍証が得られた点である。本研究成果はFSGSの液性因子同定に資するものであり、今後の診断法や治療法の開発に貢献した点で社会的意義がある。