2004 Fiscal Year Final Research Report Summary
Mechanisms of attenuation of renal injury in biglycan transgenic mice
| Project/Area Number |
14571036
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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 | Keio University |
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Principal Investigator |
SASAMURA Hiroyuki Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (00235293)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Matsuhiko Keio University, Department of Medicine, Associate Professor, 医学部, 助教授 (60129608)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Biglycan / Proteoglycan / Kidney / Fibrosis |
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| Research Abstract |
In this study, the human biglycan cDNA was ligated downstream of the alpha-smooth muscle actin promoter to produce biglycan transgenic mice. In the aorta and renal vasculature, increased vascular proliferation was seen both in the basal state and after infusion of angiotensin II (Ang II) in the transgenic mice compared to wild-type controls. In vitro, biglycan caused an increase in thymidine incorporation and migration of vascular smooth muscle cells, whereas these parameters were unchanged or reduced in endothelial cells. Next, we examined the effects of biglycan overexpression on the development of renal interstitial fibrosis following unilateral ureteral obstruction (UUO). UUO resulted in an increase in renal interstitial fibrosis, however expression of type 1 collagen was reduced in the transgenic mice compared to their wild-type littermates, with a similar trend for fibronectin and TGF-β1. Moreover TGF-β1-induced proliferation of cultured fibroblasts was reduced by biglycan pretreatment. These results suggest that, in contrast to the actions in the vasculature, biglycan overexpression in the renal interstitium results in an attenuation of renal fibrosis via a mechanism involving interactions with TGF-β1.
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Research Products
(12 results)
