卢米坎
基质凝胶
血管生成
基质金属蛋白酶
化学
细胞生物学
整合素
蛋白多糖
体内
分子生物学
内皮干细胞
细胞外基质
生物
体外
细胞
生物化学
癌症研究
生物技术
多糖
作者
Jolanta Niewiarowska,Stephane Brézillon,Izabela Sacewicz‐Hofman,Radosław Bednarek,François‐Xavier Maquart,Mariusz Malinowski,Magdalena Wiktorska,Yanusz Wegrowski,Czesław S. Cierniewski
标识
DOI:10.1016/j.thromres.2011.06.011
摘要
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 and methods 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 β1 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 α2β1 receptor activity and downregulating proteolytic activity associated with surface membranes of endothelial cells.
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