2001 Fiscal Year Final Research Report Summary
Investigation of Integrin-mediated MAP kinase Signaling in Glomerulonephritis
| Project/Area Number |
12670756
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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 |
Pediatrics
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KAGAMI Shoji University Hospital, The University of Tokushima, Assistant Professor, 医学部・附属病院, 講師 (00224337)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Yasuhiro School of Medicine, The University of Tokushima, Professor, 医学部, 教授 (20035471)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Integrin / ECM remodeling / ERK signaling / Glomerular sclerosis |
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| Research Abstract |
In order to control the function and behaviors of glomerular mesangial cell(MC) in progressive glomerulonephritis(GN), we investigated the integrin-mediated cell signaling pathway involved in MC adhesion on extracellular matrix (ECM). Cell proliferation, migration and collagen contraction assays revealed that α1β1 integrin -mediated ERK/AP-1 signaling is important pathway for pathological ECM remodeling seen in progressive GN. Either function-blocking antibody, ERK inhibitor (PD98059) or dominant negative c-jun vector (TAM67) inhibited α1β1 integrin -mediated ERK/AP-1 signaling in MC-induced pathological ECM remodeling. Administration of function-blocking anti- α1 integrin antibody into rats with anti-Thy-1 GN showed histological improvement with respect to MC proliferation and abnormal ECM remodeling compared with control anti-Thy-1 GN rats received control antibody. These results indicate that MC- α1β1 integrin- mediated ERK/AP-1 signaling play a critical role in pathological ECM remodeling in progressive GN.
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Research Products
(6 results)
