Establishment of a Novel Membranous Nephropathy Model and Investigation of Pathomechanisms - Toward Development of Treatment Strategy -

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17247
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kyoto University
• Principal Investigator: Keiko YASUDA 京都大学, 医学研究科, 特定助教 (00836265)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 自己免疫疾患 / 膜性腎症

Outline of Final Research Achievements

Membranous nephropathy has long been described as "idiopathic" with no specific cause, but a total of six causative antigens have been reported, including PLA2R, THSD7A, EXT1/EXT2, NELL-1, Semaphorin3B, and HTRA1, and it is now clear that it is an autoimmune disease. Focusing on THSD7A, the researchers induced antibody production in THSD7A-deficient mice, and confirmed that THSD7A auto antibodies can induce membranous nephropathy using a cell transfer system. This achievement is expected to contribute greatly to the establishment of a basis for investigating the pathogenesis of membranous nephropathy, for which there has been no appropriate mouse model to date.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

末期腎不全により、血液透析といった腎代替療法を要する患者は増加の一途をたどり、2020年末の日本透析学会の集計では慢性透析患者は33万6千人を超えている。透析療法の技術向上や、透析患者の死因となる心血管イベントの抑制としてCKD-MBD(Chronic Kidney Disease-Mineral and Bone Disorder)という概念が確立され、透析導入後の生命予後が改善する一方で、透析導入を抑制、遅延する腎臓病の根本治療薬は依然としてない。今回、膜性腎症のマウスモデルを新規に確立した。病態を理解するための基盤構築を引き続き行い、病態の即した新規の治療法の開発を目指す。