Elucidation of the function of podocyte-specific gene CRB2 in the development of focal segmental glomerulosclerosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08255
• 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: Mie University
• Principal Investigator: Katayama Kan 三重大学, 医学部附属病院, 准教授 (90742247)
• Co-Investigator(Kenkyū-buntansha): 土肥 薫 三重大学, 医学系研究科, 教授 (50422837)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 巣状分節性糸球体硬化症 / ポドサイト / タンパク尿 / アルブミン尿 / 血尿

Outline of Final Research Achievements

The role of the CRB2 gene in the development of focal segmental glomerulosclerosis was elucidated by generating podocyte-specific Crb2 knockout mice before and after birth. In the prenatal mouse model, severe albuminuria and hematuria were exhibited at 2 months of age, progression of glomerulosclerosis and interstitial fibrosis, and fusion of foot processes were observed by electron microscopy at 6 months of age, which was associated with decreased expression of various podocyte-related proteins. Cultured human CRB2 knockout podocytes were prone to apoptosis. In the postnatal mouse model, not only did it exhibit severe albuminuria and hematuria 2 months after intraperitoneal administration, but also progression of glomerulosclerosis and interstitial fibrosis, and fusion of foot processes were observed under electron microscopy at 4 months after administration.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

巣状分節性糸球体硬化症(FSGS)は難治性疾患となることが多く、成人発症FSGSの一部はポドサイトの単一遺伝子異常が原因である遺伝性FSGSと判明している。今回の研究により、CRB2遺伝子がFSGS発症に関係するポドサイト関連遺伝子であることがマウスモデルで解明されたため、このマウスモデルを用いて新規の治療薬開発が進むと考えられる。