Osteoprotegerin is an alpha vbeta 3-induced, NF-kappa B-dependent survival factor for endothelial cells.
Osteoprotegerin is an alpha vbeta 3-induced, NF-kappa B-dependent survival factor for endothelial cells.
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发表时间：
2000
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通讯作者：
U. Malyankar;M. Scatena;K. Suchland;T. Yun;E. Clark;C. Giachelli
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作者：
U. Malyankar;M. Scatena;K. Suchland;T. Yun;E. Clark;C. Giachelli
骨桥蛋白保护内皮细胞免受生长因子撤除诱导的凋亡。这种相互作用由α（v）β（3）整联蛋白介导，并且是NF-κ B依赖性的（Scatena，M.，Almeida，M.，Chaisson，M. L.，Fausto，N.，尼科西亚河F.、和Giachelli，C. M.等（1998）J. Cell Biol.141，1083-1093）。在本研究中，我们使用差异克隆来鉴定内皮细胞中骨桥蛋白诱导的NF-κ B依赖性基因。其中一个基因是骨保护素，它是肿瘤坏死因子受体超家族的一员。通过北方和Western印迹分析，骨保护素mRNA和蛋白水平在铺在非整合素细胞附着因子聚-d-赖氨酸上的内皮细胞中非常低。相比之下，骨桥蛋白α（v）β（3）连接后，骨保护素mRNA和蛋白水平诱导5-7倍。骨桥蛋白诱导骨保护素是时间依赖性的，并观察到早在治疗后3小时。通过在内皮细胞中过度表达IkappaB超阻遏物实现NF-κ B失活，完全抑制骨桥蛋白对骨保护素的诱导。最后，纯化的骨保护素保护具有失活NF-κ B的内皮细胞免受生长因子剥夺诱导的凋亡。这些数据表明，alpha（v）beta（3）介导的内皮细胞存活取决于NF-κ B对骨保护素的诱导，并表明骨保护素在内皮细胞中的新功能。
Osteopontin protects endothelial cells from apoptosis induced by growth factor withdrawal. This interaction is mediated by the alpha(v)beta(3) integrin and is NF-kappaB-dependent (Scatena, M., Almeida, M., Chaisson, M. L., Fausto, N., Nicosia, R. F., and Giachelli, C. M. (1998) J. Cell Biol. 141, 1083-1093). In the present study we used differential cloning to identify osteopontin-induced, NF-kappaB-dependent genes in endothelial cells. One of the genes identified in this screen was osteoprotegerin, a member of the tumor necrosis factor receptor superfamily. By Northern and Western blot analysis, osteoprotegerin mRNA and protein levels were very low in endothelial cells plated on the non-integrin cell attachment factor, poly-d-lysine. In contrast, osteoprotegerin mRNA and protein levels were induced 5-7-fold following alpha(v)beta(3) ligation by osteopontin. Osteoprotegerin induction by osteopontin was time-dependent and observed as early as 3 h following treatment. NF-kappaB inactivation achieved by over expression of an IkappaB super repressor in endothelial cells completely inhibited osteoprotegerin induction by osteopontin. Finally, purified osteoprotegerin protected endothelial cells with inactive NF-kappaB from apoptosis induced by growth factor deprivation. These data suggest that alpha(v)beta(3)-mediated endothelial survival depends on osteoprotegerin induction by NF-kappaB and indicate a new function for osteoprotegerin in endothelial cells.