Lumican inhibits angiogenesis by interfering with α2ß1 receptor activity and downregulating MMP-14 expression.
Thromb Res
; 128(5): 452-7, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21752432
ABSTRACT
INTRODUCTION:
Previous studies showed that lumican, a small leucine-rich proteoglycan that binds to α2 integrin I domain, is an efficient inhibitor of cell adhesion and migration. In this report, we tested its effect on angiogenesis in vitro and in vivo. MATERIALS ANDMETHODS:
Effect of lumican on angiogenesis was evaluated by in vitro capillary tube formation test performed between Fibrin II Gels or in Matrigel™ and in vivo by Matrigel(™) plug assay in BALB/c mice. Changes in matrix metalloproteinases expression caused by lumican were analyzed in endothelial cells by real-time PCR, Western immunoblotting and gelatin zymography.RESULTS:
In unchallenged endothelial cells, Matrigel™ induced robust capillary morphogenesis. In contrast, tube formation was dramatically reduced by lumican, and by siRNA to ß1 integrin subunit mRNA but not by control siRNA. Similarly, lumican effectively inhibited neovascularization in vivo in assays using Matrigel™ plugs formed in BALB/c mice. Interestingly, lumican significantly reduced expression of matrix metalloproteinases, particularly MMP-14 that is known to activate other MMPs in close vicinity of endothelial cell membranes.CONCLUSIONS:
Our results provide strong evidence that lumican affects angiogenesis both by interfering with α2ß1 receptor activity and downregulating proteolytic activity associated with surface membranes of endothelial cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteoglicanas de Sulfatos de Condroitina
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Neovascularização Fisiológica
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Integrina alfa2beta1
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Inibidores de Metaloproteinases de Matriz
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Sulfato de Queratano
Limite:
Animals
Idioma:
En
Revista:
Thromb Res
Ano de publicação:
2011
Tipo de documento:
Article