Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin αVβ3
Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin αVβ3
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DOI：
10.1074/jbc.m203889200
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发表时间：
2002-06-28
影响因子：
4.8
通讯作者：
Pohl, U
中科院分区：
文献类型：
--
作者：
Gloe, T;Sohn, HY;Pohl, U
考虑到剪切应力的慢性升高导致血管的重塑，我们分析了机械负荷是否可以介导碱性成纤维细胞生长因子（bFGF）的释放，以及bFGF是否可以作为剪切应力诱导的内皮细胞增殖和分化的介质。剪切应力暴露的内皮细胞（EC）上清培养基中bFGF的含量明显高于静态细胞培养基。释放的bFGF作为诱导增殖和分化的功能是完全完整的。剪切应力条件下的介质诱导了毛细管状结构的形成，而静态控制介质则没有。同样，只有剪应力条件培养基才能诱导血清饥饿EC的增殖。中和bFGF或其受体可抑制毛细血管样结构的形成和增殖。bFGF的释放受到特异性整合素介导的控制，因为α (v) β(3)整合素的抑制阻止了它的释放，而α (5) β(1)整合素的抑制没有影响。我们得出结论，剪切应力诱导bFGF以严格控制的方式从EC中释放。释放依赖于通过α (v) β(3)整合素的特定细胞-基质相互作用。对细胞增殖和分化的影响表明，bFGF的释放在功能上是显著的，可能是剪切应力诱导的适应性重塑过程中必要的第一步。
Considering that chronic elevation of shear stress results in remodeling of the vasculature, we analyzed whether mechanical load could mediate basic fibroblast growth factor (bFGF) release and whether bFGF would act as mediator of shear stress-induced endothelial proliferation and differentiation. Supernatant media of shear stress-exposed endothelial cells (EC) contained significantly higher amounts of bFGF than medium from static cells. Released bFGF was fully intact with regard to its function as an inductor of proliferation and differentiation. Shear stress-conditioned media induced capillary-like structure formation, whereas static control medium did not. Likewise, only shear stress-conditioned medium induced proliferation of serum starved EC. Both capillary-like structure formation and proliferation could be inhibited by neutralization of bFGF or its receptor. The release of bFGF was subject to specific, integrin-mediated control, since inhibition of alpha(v)beta(3) integrin prevented it, whereas inhibition of alpha(5)beta(1) integrin had no effect. We conclude that shear stress induces the release of bFGF from EC in a tightly controlled manner. The release is dependent on specific cell-matrix interactions via alpha(v)beta(3) integrins. The effects on cell proliferation and differentiation suggest that release of bFGF is functionally significant and may represent a necessary initial step in adaptive remodeling processes induced by shear stress.