Opticin exerts its anti-angiogenic activity by regulating extracellular matrix adhesiveness.
Opticin exerts its anti-angiogenic activity by regulating extracellular matrix adhesiveness.
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Opticin 通过调节细胞外基质粘附性发挥其抗血管生成活性。
DOI：
10.1074/jbc.m111.331157
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发表时间：
2012-08-10
期刊：
影响因子：
--
通讯作者：
Bishop PN
中科院分区：
文献类型：
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作者：
Le Goff MM;Sutton MJ;Slevin M;Latif A;Humphries MJ;Bishop PN
背景：最近，我们发现糖蛋白opticin具有抗血管生成的作用。在这里，基础机制进行了探讨。结果：通过与胶原蛋白结合，光学蛋白竞争性抑制整合素介导的内皮细胞粘附。结论：Opticin通过减弱内皮细胞与周围细胞外基质的粘附来抑制血管生成。意义：阐明血管生成的调节机制对于理解病理学和药物发现非常重要。视蛋白是一种细胞外基质糖蛋白，我们发现它与眼睛玻璃体液的胶原网络有关。最近，我们发现opticin具有抗血管生成活性，使用小鼠氧诱导的视网膜病变模型：在这里，我们调查的潜在机制。使用离体鸡胚绒毛尿囊膜测定，我们表明，opticin抑制血管生成时，刺激了一系列的生长因子。我们发现，它抑制毛细血管形态发生，抑制内皮细胞的侵袭，并促进毛细血管网络的胶原蛋白和MatrigelTM的三维矩阵的回归。然后，我们表明，opticin结合胶原蛋白，从而竞争性地抑制内皮细胞与胶原蛋白通过α1β1和α2β1整合素的相互作用，从而防止强粘附，所需的促血管生成信号通过这些整合素。
Background: Recently, we demonstrated that the glycoprotein opticin is anti-angiogenic. Here, the underpining mechanism is explored. Results: By binding to collagen, opticin competitively inhibits integrin-mediated endothelial cell adhesion. Conclusion: Opticin inhibits angiogenesis by weakening endothelial cell adhesion to the surrounding extracellular matrix. Significance: Elucidating the regulatory mechanisms of angiogenesis is important for understanding pathology and drug discovery. Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. Recently, we discovered that opticin possesses anti-angiogenic activity using a murine oxygen-induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and MatrigelTM. We then show that opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via α1β1 and α2β1 integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins.