Endoglin regulates mural cell adhesion in the circulatory system.
Endoglin regulates mural cell adhesion in the circulatory system.
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DOI：
10.1007/s00018-015-2099-4
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Bernabeu C
中科院分区：
文献类型：
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作者：
Rossi E;Smadja DM;Boscolo E;Langa C;Arevalo MA;Pericacho M;Gamella-Pozuelo L;Kauskot A;Botella LM;Gaussem P;Bischoff J;Lopez-Novoa JM;Bernabeu C
循环系统由不同类型的细胞组成，包括血管壁细胞和足细胞。内皮细胞（EC）和壁细胞（如血管平滑肌细胞或周细胞）之间的相互作用和相互作用在血管生物学中起着关键作用。Endoglin是β1整合素的含RGD的反受体，在血管生成过程中由EC高度表达。我们发现血管内皮细胞和壁细胞之间的粘附通过整合素激活剂增强，并且在抑制膜内皮糖蛋白或β1-整合素时以及通过添加可溶性内皮糖蛋白（SolEng）、抗整合素α5β1抗体或RGD肽来抑制。不同的内皮糖蛋白突变体的分析，允许参与粘附过程的内皮糖蛋白RGD基序的映射。在Eng+/−小鼠（遗传性出血性毛细血管扩张症1型模型）中，内皮联蛋白单倍不足诱导周细胞依赖性血管通透性增加。此外，过度表达SolEng的转基因小鼠（先兆子痫的动物模型）显示足细胞尿，表明SolEng负责足细胞从肾小球毛细血管脱离。这些结果表明内皮糖蛋白在整合素介导的壁细胞粘附中起关键作用，并提供了对正常生理学以及病理学（如先兆子痫或遗传性出血性毛细血管扩张症）中血管成熟机制的更好理解。本文的在线版本（doi：10.1007/s 00018 -015-2099-4）包含补充材料，可供授权用户使用。
The circulatory system is walled off by different cell types, including vascular mural cells and podocytes. The interaction and interplay between endothelial cells (ECs) and mural cells, such as vascular smooth muscle cells or pericytes, play a pivotal role in vascular biology. Endoglin is an RGD-containing counter-receptor for β1 integrins and is highly expressed by ECs during angiogenesis. We find that the adhesion between vascular ECs and mural cells is enhanced by integrin activators and inhibited upon suppression of membrane endoglin or β1-integrin, as well as by addition of soluble endoglin (SolEng), anti-integrin α5β1 antibody or an RGD peptide. Analysis of different endoglin mutants, allowed the mapping of the endoglin RGD motif as involved in the adhesion process. In Eng+/− mice, a model for hereditary hemorrhagic telangectasia type 1, endoglin haploinsufficiency induces a pericyte-dependent increase in vascular permeability. Also, transgenic mice overexpressing SolEng, an animal model for preeclampsia, show podocyturia, suggesting that SolEng is responsible for podocytes detachment from glomerular capillaries. These results suggest a critical role for endoglin in integrin-mediated adhesion of mural cells and provide a better understanding on the mechanisms of vessel maturation in normal physiology as well as in pathologies such as preeclampsia or hereditary hemorrhagic telangiectasia. The online version of this article (doi:10.1007/s00018-015-2099-4) contains supplementary material, which is available to authorized users.