Inhibitory effects of recombinant RTS-jerdostatin on integrin 伪1尾1 function during adhesion, migration and proliferation of rat aortic smooth muscle cells and angiogenesis
详细信息 查看全文
- 作者：Gema Bol谩s ; Fl谩via Figueiredo de Rezende ; Carolina Lorente ; Libia Sanz ; Johannes A. Eble ; Juan J. Calvete
- 关键词：Recombinant RTS disintegrin ; Jerdostatin ; 伪1尾1 integrin inhibitor ; Cell adhesion ; Angiogenesis
- 刊名：Toxicon
- 出版年：1 March, 2014
- 年：2014
- 卷：79
- 期：Complete
- 页码：45-54
- 全文大小：1296 K
文摘
Jerdostatin, a short RTS-disintegrin cloned from venom gland mRNA of Protobothrops jerdonii, selectively blocks the adhesion of 伪1尾1 integrin to collagen IV. Integrin 伪1尾1 is highly expressed in smooth muscle cells (SMC) surrounding small blood vessels and vascular endothelial cells. Vascular SMC adhesion, migration and proliferation are important processes during normal vascular development. Using recombinant jerdostatin we have investigated the role of the 伪1尾1 integrin on the adhesion of vascular SMC to collagen IV, and the potential relevance of blocking this crucial component of focal adhesions as an anti-angiogenic strategy. Our results show that jerdostatin does not interact with canonical collagen-binding site on the isolated A-domain of the 伪1 integrin subunit. r-Jerdostatin inhibited the adhesion of RASMCs to immobilized CB3 fragment in a dose-dependent manner, triggering to round-up, retraction, and finally detachment of the cells. r-Jerdostatin did not affect the adhesion of human SMCs to CB3, presumably because the high expression of 伪2尾1 integrin compensated for 伪1尾1 integrin blockage by jerdostatin. r-Jerdostatin dose-dependently inhibited 伪1尾1 integrin-dependent HUVEC tube formation. However, VEGF-driven tube formation in the matrigel assay was only completely abolished when binding of integrin 伪2尾1 to collagen was also inhibited by the C-type lectin-like rhodocetin. As a whole, our work emphasizes the relevance of using specific inhibitors for dissecting the role of 伪1尾1 integrin in physiological and pathological conditions.