| Project/Area Number |
14570748
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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 The University of Tokushima, University Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (00224337)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIZUMI Masanori The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 講師 (60294667)
KURODA Yasuhiro The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (20035471)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Integrin / ECM remodeling / ERK-AP1 signaling / Glomerular sclerosis / ILK / ラット抗Thy-1腎炎 / MMP / エンドセリン |
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| Research Abstract |
In order to prevent the progression of renal diseases, we investigated the role of collagen-binding integrin receptor in the development of renal fibrosis. Cell proliferation, migration and collagen contraction assays revealed that both alf3l integrin-mediated ERK/AP-1 and lintegrin-linked kinase (ILK)signalings are important pathways for pathological ECM remodeling seen in progressive glomerulonephritis (GN). Either function-blocking antibody, ERK inhibitor (PD98059) or dominant negative cDNA vector inhibited integrin-mediated signaling on in vitro ECM remodeling seen in progressive GN. Administration of integrin 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 integrin-mediated signaling pathways play a critical role in pathological ECM remodeling in progressive renal fibrosis.
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