Role of complement 3 in the pathogenesis of hypertension

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nihon University
• Principal Investigator: FUKUDA Noboru 日本大学, 総合科学研究科, 教授 (40267050)
• Co-Investigator(Kenkyū-buntansha): UENO Takahiro 日本大学, 医学部, 准教授 (40386008)
• Co-Investigator(Renkei-kenkyūsha): NISHIYAMA Akira 香川大学, 医学部, 教授 (10325334) ; MASHIMO Tomoji 京都大学, 医歯学系, 准教授 (80397554)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 高血圧 / 補体 / ジンクフィンガーヌクレアーゼ / 高血圧自然発症ラット

Outline of Final Research Achievements

We investigated role of C3 in phenotype of mesenchymal cells and renal RA in SHR in vitro and in vivo. We investigated expression of renal C3, renin, TGF-β1 and LXRα and generation of Ang II in kidney of UUO model that shows EMT in C3 KO mice. We knock outed C3 gene from SHR/Izm by the zinc-finger nucleaze method and investigated blood pressure and phenotype in SHR. In wild type mice, C3 and renin were strongly stained in the degenerated nephrotubulus at same localization with increases in expression of C3 renin with increases in blood pressure in UUO model. In C3 KO mice, the EMT phenomen was suppressed with no expression of renin in UUO model. Blood pressure and body weight were significantly lower in C3 KO SHR. C3 is involved in the cardiovascular and renal remodelings in hypertension. C3 induces EMT of nephrotubulus and activation of renal RA system. C3 is a primary factor to activate the renal RA systems to induce hypertension in SHR.

Free Research Field

高血圧学