Involvement of C3 in the pathogenesis of hypertension with an activation of tissue renin-angiotensin system
| Project/Area Number |
15K09300
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Nihon University |
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Principal Investigator |
FUKUDA Noboru 日本大学, 総合科学研究所, 教授 (40267050)
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| Co-Investigator(Kenkyū-buntansha) |
上野 高浩 日本大学, 医学部, 兼任講師 (40386008)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMATSU Kazutoshi 日本大学, 医学部, 客員教授 (50297800)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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 / ジンクフィンガーヌクレアーゼ |
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| 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.
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Report
(4 results)
Research Products
(22 results)
