Exploration of the mechanisms underlying normal glomerular filtration function and its pathologic disruption via the TRPC6-slit diaphragm protein complex-mediated mechano-signaling

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390054
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Fukuoka University
• Principal Investigator: Inoue Ryuji 福岡大学, 医学部, 教授 (30232573)
• Co-Investigator(Renkei-kenkyūsha): MORI Masayuki 京都大学, 工学部, 准教授 (80342640)
• Research Collaborator: KURAHARA Lin-Hai ; ICHIKAWA Jun ; HU Yaopeng
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 腎スリット膜複合体 / 機械刺激情報伝達 / TRP蛋白質 / Ca情報伝達 / 糸球体硬化症

Outline of Final Research Achievements

To explore the precise physiological and pathophysiological implications of the slit diaphragm complex including a canonical member of transient receptor potential (TRP) channel TRPC6, in regulating the glomerular filtration function, we carried out detailed analysis with a minimally constructed slit-diaphragm-protein expression system and a ‘pseudo-slit diaphragm’ formed by podocytes on an artificial filter membrane. The results have suggested that the complex of TRPC6-podocin-(nephrin)-cytoskeletal actin mediates Ca influx into renal podocytes in response to receptor and mechanical stimuli, thereby effectively regulating the glomerular barrier function, and that conditions causing the excess of these Ca responses such as mutations associated with familial focal glomerulosclerosis and renal inflammation, may lead to disruption of the barrier and subsequent proteinuria.

Free Research Field

分子病態生理学、システム分子生理学