In:
Diabetes, American Diabetes Association, Vol. 58, No. 10 ( 2009-10-01), p. 2365-2375
Abstract:
The involvement of proangiogenic factors such as vascular endothelial growth factor as well as the therapeutic efficacy of angiogenesis inhibitors in early diabetic nephropathy has been reported. Vasohibin-1 (VASH-1) is a unique endogenous angiogenesis inhibitor that is induced in endothelial cells by proangiogenic factors. We investigated the therapeutic efficacy of VASH-1 in an early diabetic nephropathy model. RESEARCH DESIGN AND METHODS Streptozotocin- induced type 1 diabetic mice received intravenous injections of adenoviral vectors encoding VASH-1 (AdhVASH-1) or β-gal (AdLacZ) every other week and were killed after 28 days. RESULTS Treatment with AdhVASH-1 resulted in sustained increase in the protein levels of VASH-1 in the liver and sera, in the absence of any inflammatory alterations. AdhVASH-1 treatment significantly suppressed renal hypertrophy, glomerular hypertrophy, glomerular hyperfiltration, albuminuria, increase of the CD31+ glomerular endothelial area, F4/80+ monocyte/macrophage infiltration, the accumulation of type IV collagen, and mesangial matrix compared with AdLacZ-treated diabetic mice. Increase in the renal levels of transforming growth factor-β1, monocyte chemoattractant protein-1, and receptor for advanced glycation end products in diabetic animals was significantly suppressed by AdhVASH-1 (real-time PCR and immunoblot). VASH-1 significantly suppressed the increase of transforming growth factor-β, monocyte chemoattractant protein-1, and receptor for advanced glycation end products, induced by high ambient glucose in cultured mouse mesangial cells. Increased phosphorylation of VEGFR2 was suppressed in AdVASH-1–treated diabetic animals and in cultured glomerular endothelial cells. Endogenous mouse VASH-1 was localized to the mesangial and endothelial area in glomeruli of diabetic mice. CONCLUSIONS These results suggest the potential therapeutic efficacy of VASH-1 in treating early diabetic nephropathy potentially mediated via glomerular endothelial and mesangial cells.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2009
detail.hit.zdb_id:
1501252-9
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