Involvement of C3 in the pathogenesis of hypertension with an activation of tissue renin-angiotensin system

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09300
• 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, 総合科学研究所, 教授 (40267050)
• Co-Investigator(Kenkyū-buntansha): 上野 高浩 日本大学, 医学部, 兼任講師 (40386008)
• Co-Investigator(Renkei-kenkyūsha): KOMATSU Kazutoshi 日本大学, 医学部, 客員教授 (50297800)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 高血圧 / 補体 / ゲノム編集 / 高血圧自然発症ラット / 形質変換

Outline of Final Research Achievements

We established C3 KO SHR by the gene editing technology ZFN method and investigated blood pressure, histological changes and gene expression in kidney and renal RA systems. SHR showed salt-sensitive hypertension that was abolished in C3 KO SHR. Expression of E-cadhelin was suppressed in renal medulla from SHR indicating EMT phenomen that was not observed in kidney from C3 KO SHR. Intrarenal Ang II was increased with a salt-loading in SHR, which was suppressed in C3 KO SHR. During the differenciation of C3 KO mouse-derived mesenchymal stem cells to vascular smooth muscle cells, renin was transiently expressed with C3, KLF-5 and LXRa. These findings indicate that complement 3 induces EMT phenomen of nephrotubulus and enhances the intrarenal RA system to induce the salt-sensitive hypertension.

Free Research Field

高血圧学