Vasohibin-1, a negative feedback regulator of angiogenesis, ameliorates renal alterations in a mouse model of diabetic nephropathy.
Diabetes
; 58(10): 2365-75, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19587360
ABSTRACT
OBJECTIVE:
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 ANDMETHODS:
Streptozotocin- induced type 1 diabetic mice received intravenous injections of adenoviral vectors encoding VASH-1 (AdhVASH-1) or beta-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-beta1, 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-beta, 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
/
Inibidores da Angiogênese
/
Nefropatias Diabéticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2009
Tipo de documento:
Article