2006 Fiscal Year Final Research Report Summary
Effect of macrophages transferred with angiotensin II receptor gene on the evolution of renal fibrosis
| Project/Area Number |
17591107
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NISHIDA Masashi Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教 (50275202)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAOKA Kenji Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (60189602)
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| Project Period (FY) |
2005 – 2006
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| Keywords | renal fibrosis / macrophage / unilateral ureteral obstruction / angiotensin II type 1 receptor |
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| Research Abstract |
We examined the in vivo function of the angiotensin II type 1 receptor (Agtr1) on macrophages in renal fibrosis. Fourteen days after the induction of unilateral ureteral obstruction (UUO), wild-type mice reconstituted with marrow lacking the Agtrl gene (Agtr1^<-/->) developed more severe interstitial fibrosis with fewer interstitial macrophages than those in mice reconstituted with Agtrl^<+/+> marrow. These differences were not observed at day 5 of UUO. The expression of profibrotic genes-including TGF-β1, α1(I) collagen, and α1(III) collagen-was substantially higher in the obstructed kidneys of mice with Agtr1^<-/->marrow than in those with Agtrl^<+/+> marrow at day 14 but not at day 5 of UUO. Mice with Agtr1^<-/->marrow were characterized by reduced numbers of peripheral-blood monocytes and macrophage progenitors in bone marrow. In vivo assays revealed a significantly impaired phagocytic capability in Agtr1^<-/->macrophages. In vivo treatment of Agtr1^<+/+> mice with losartan reduced phagocytic capability of Agt1^<+/+> macrophages to a level comparable to that of Agtrl^<-/->macrophages. Thus, during urinary tract obstruction, the Agtrl on bone marrow-derived macrophages functions to preserve the renal parenchymal architecture, and this function depends in part on its modulatory effect on phagocytosis.
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