THE INTEGRIN-ASSOCIATED SIGNAL TRANSDUCTION IN GLOMERULAR MESANGIAL CELLS IN THE PROGRESSION OF GLOMERULAR DISEASES
| Project/Area Number |
15590839
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
OOTAKA Tetsuya TOHOKU UNIVERSITY, SCHOOL OF HEALTH SCIENCES, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (70271921)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Hiroshi TOHOKU UNIVERSITY, HOSPITAL, LECTURER, 病院・講師 (60215829)
NAKAYAMA Kenji TOHOKU UNIVERSITY, HOSPITAL, RESEARCH ASSOCIATE, 病院・助手 (90344671)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | crescentic glomerulonephritis / membranoproliferative glomerulonephritis / IgA nephropathy / glomerular mesangial cells / glomerular epithelial cells / integrins / signal transduction / 細胞外基質蛋白 |
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| Research Abstract |
An immunohistochemical study was performed on renal biopsy specimens to detect the glomerular expression of beta1 and beta3 integrins and that of integrin-related signal transduction proteins. In the cases of crescentic glomerulonapheitis, cellular crescents showed strong expression of beta1/alpha3 and beta3/alphaV integrins together with intense deposition of fibronectin (FN). At the same time, the expression of the following integrin-related signal transduction proteins was observed in cellular crescents ; FAK, c-Src, PI3K, Akt1, Raf1, Rac1 and RhoA. The staining of all these proteins was decreased or diminished in fibrocellular or fibrous crescents. These findings indicated that beta1/alpha3 and beta3/alphaV integrins function as FN receptor. The binding of FN with these integrins may induce the activation of integrin-related signal transduction proteins such as FAK, c-Src, PI3K and then the signal proteins in lower stream such as Raf, Akt and Rac/Rho, which might be involving in the cell survival and cell growth in cellular crescents. In the cases of membranoproliferative glomerulonephritis (MPGN) and IgA nephropathy (IgAN), mesangaial cells showed the expression of beta1/alpha3 and beta1/alpha3 integrins together with enhanced deposition of collagen type IV (CL IV) and FN, suggesting the interaction of CL IV or FN with those beta1 integrins. On the other hand, only FAK, Akt1 and RhoA were expressed mildly in mesangium in these diseases.
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Report
(4 results)
Research Products
(9 results)
