Exploration of the mechanisms underlying normal glomerular filtration function and its pathologic disruption via the TRPC6-slit diaphragm protein complex-mediated mechano-signaling
Project/Area Number |
24390054
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
General physiology
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Research Institution | Fukuoka University |
Principal Investigator |
Inoue Ryuji 福岡大学, 医学部, 教授 (30232573)
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Co-Investigator(Renkei-kenkyūsha) |
MORI Masayuki 京都大学, 工学部, 准教授 (80342640)
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Research Collaborator |
KURAHARA Lin-Hai
ICHIKAWA Jun
HU Yaopeng
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
|
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 / スリット膜複合体 / 受容体刺激・機械刺激情報伝達 / 足細胞 / 濾過機能 / PKGリン酸化 / 受容体刺激情報伝達 |
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.
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Report
(5 results)
Research Products
(52 results)
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[Journal Article] Screening of TRPC Channel Activators Identifies Novel Neurotrophic Piperazine Compounds2016
Author(s)
Sawamura S, Hatano M, Takada Y, Hino K, Kawamura T, Tanikawa J, Nakagawa H, Hase H, Nakao A, Hirano M, Rotrattanadumrong R, Kiyonaka S, Mori MX, Nishida M, Hu Y, Inoue R, Nagata R, Mori Y
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Journal Title
Molecular Pharmacology
Volume: 89
Pages: 348-363
DOI
Related Report
Peer Reviewed
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[Journal Article] BDNF induces sustained intracellular Ca2+ elevation through the upregulation of surface TRPC3 channels in rodent microglia.2014
Author(s)
Mizoguchi Y, Kato TA, Seki Y, Ohgidani M, Sagata N, Horikawa H, Yamauchi Y, Sato-Kasai M, Hayakawa K, Inoue R, Kanba S, Monji A.
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Journal Title
Journal of Biological Chemistry
Volume: 289
Pages: 18549-55
DOI
Related Report
Peer Reviewed
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[Presentation] Mutagenic and post-translational modifications of the mechanosensitivity of reno-cardiovascular TRPC6 channel2014
Author(s)
Inoue, R., Jian, Z., Ichikawa, J., Nakagawa, M., Kurahara, L., Hu Y.
Organizer
The 2nd International Symposium of Mechanobiology
Place of Presentation
Okayama
Year and Date
2014-05-22
Related Report
Invited
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