2005 Fiscal Year Final Research Report Summary
Clarification of multi-functions of macrophage populations in renal fibrosis and therapeutic strategies
| Project/Area Number |
15380217
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical veterinary science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
YAMATE Jyoji Osaka Prefecture University, Life and Environmental Sciences, Associate Professor, 生命環境科学研究科, 助教授 (50150115)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAMURA Mitsuru Osaka Prefecture University, Life and Environmental Sciences, Assistant Professor, 生命環境科学研究科, 講師 (20244668)
TSUKAMOTO Yasuhiro Osaka Prefecture University, Life and Environmental Sciences, Associate Professor, 生命環境科学研究科, 助教授 (90305657)
KUMAGAI Daijirou Osaka Prefecture University, Life and Environmental Sciences, Research Assistant, 生命環境科学研究科, 助手 (70316016)
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| Project Period (FY) |
2003 – 2005
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| Keywords | renal fibrosis / macrophage / myofibroblast / fibrogenic factor / cisplatin / dexamethasone / hepatic fibrosis / rat model |
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| Research Abstract |
The purposes of this study were to clarify the functional roles of macrophages appearing in the renal fibrosis, and to explore the useful therapeutic strategies for the intractable diseases, on the basis of the data.
Dexamethasone (DX), an anti-inflammatory drug, was injected in rat models of chronic renal fibrosis induced by cisplatin. As a result, the DX injection decreased the number of ED1-positive exudate macrophages, leading to the reduction of the progressive renal fibrosis. However, the appearance of ED2-positive resident macrophages and OX6-positive antigen presenting macrophages were not influenced by the DX injection. In addition, the concomitant addition of TGF-β1 (a fibrogenic factor) and DX to rat renal interstitial cells (NRK-49F) and rat undifferentiated mesenchymal cells (MT-9) decreased the number of cells reacting to α-smooth muscle actin (α-SMA). These findings of in vivo and in vitro studies indicate that DX ameliorates the progressive renal fibrosis through the dec
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reased number of ED1-positive macrophages and the reduction of the formation of α-SMA-positive myofibroblastic cells induced by TGF-β1. Using acute rat renal fibrosis model, the effect of dietary azuki bean (Vigna angularis) was investigated as a result, the administration with azuki bean dramatically decreased the number of ED1-positive macrophages, and reduced the renal fibrosis. It is shown nutritionally that the azuki bean may contain a substance which is able to reduce the renal fibrosis.
Using rat hepatic fibrosis model induced by thioacetoamide, of which the pathogenesis is similar to that of renal fibrosis, the influence of GdCl_3, an inhibitor of Kupffer cell functions, was investigated. As a result, the treatment with GdCl_3 reduced the number of different macrophage populations, and in particular, fibrosis around the periportal areas was improved. These data shout be referred to the understanding of the pathogenesis of renal fibrosis.
The present studies clarified some functions of macrophage populations appearing in renal fibrosis, and provided some useful therapeutic methods which may be used in human medicine, though at experimental levels. Less
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