Department of Cardiology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan 430030, China.
Int J Biochem Cell Biol. 2011 Apr;43(4):642-50. doi: 10.1016/j.biocel.2011.01.004. Epub 2011 Jan 13.
Tetraspanin CD151 mainly associates with laminin-binding integrins and forms CD151-integrin complex. We previously reported that CD151 could be a potential target for angiogenesis, but the mechanisms involved are still unclear. This study investigated the role of CD151-integrin complex in angiogenesis and the signaling mechanisms involved. Here we showed that CD151 and CD151-AAA mutant were both well expressed at the protein level. CD151 gene transfer promoted angiogenesis and improved skin temperature of the lateral ischemic hindlimb, whereas CD151-AAA mutant abrogated the increase in capillary density and skin temperature. Further, CD151-AAA mutant failed to activate the FAK, ERK, PI3K/Akt/eNOS, and Rac1/Cdc42 signaling pathways. Moreover, CD151-AAA mutant was unavailable to promote bovine aortic endothelial cells (BAECs) proliferation and migration, in contrast to the effects of CD151. The results suggested that formation of CD151-integrin complex was likely to be a prerequisite for CD151-induced angiogenesis and signaling pathways.
四跨膜蛋白 CD151 主要与层粘连蛋白结合的整合素结合，并形成 CD151-整合素复合物。我们之前的研究报道 CD151 可能是血管生成的一个潜在靶点，但涉及的机制仍不清楚。本研究探讨了 CD151-整合素复合物在血管生成中的作用及其涉及的信号机制。我们发现 CD151 和 CD151-AAA 突变体在蛋白质水平上均有良好的表达。CD151 基因转移促进血管生成，并提高缺血性后肢的皮肤温度，而 CD151-AAA 突变体则消除了毛细血管密度和皮肤温度的增加。此外，CD151-AAA 突变体不能激活 FAK、ERK、PI3K/Akt/eNOS 和 Rac1/Cdc42 信号通路。此外，与 CD151 的作用相反，CD151-AAA 突变体不能促进牛主动脉内皮细胞（BAECs）的增殖和迁移。结果表明，CD151-整合素复合物的形成可能是 CD151 诱导的血管生成和信号通路的必要前提。
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