TGF-h receptor function in the endothelium
TGF-h receptor function in the endothelium
复制标题
DOI：
--
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Franck Lebrin;Martine Deckers;Philippe Bertolino;P. Dijke
中科院分区：
文献类型：
--
作者：
Franck Lebrin;Martine Deckers;Philippe Bertolino;P. Dijke
在小鼠和人类中的遗传研究已经揭示了转化生长因子-h（TGF-h）信号传导在血管生成过程中的关键作用。各种TGF-h信号传导组分缺陷的小鼠由于血管缺陷而呈现胚胎致死性。在患者中，TGF-h I型受体ALK 1或辅助TGF-h受体内皮糖蛋白的突变与称为遗传性出血性毛细血管扩张症（HHT）的常染色体显性血管发育不良疾病有关。多年来，研究人员一直困惑于如何解释TGF h在体外和体内作为血管生成的刺激剂和抑制剂的作用。最近，已经提出了一种模型，其中TGF-β通过与TGF-β II型受体结合可以激活内皮细胞（EC）中的两种不同的I型受体，即，EC限制性ALK 1和广泛表达的ALK-5，它们对EC的行为具有相反的影响。ALK 1通过Smad 1/5转录因子刺激EC增殖和迁移，而ALK 5通过Smad 2/3抑制EC增殖和迁移。在这里，新的发现是关于发生在EC中的分子机制，以精确地调节，甚至在TGF-β诱导的生物反应之间切换。特别是，附件TGF-β受体内皮糖蛋白在EC行为的调节中的作用得到解决，并讨论了新的见解有关的可能机制，涉及HHT的发展。D 2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Genetic studies in mice and humans have revealed the pivotal role of transforming growth factor-h (TGF-h) signaling during angiogenesis. Mice deficient for various TGF-h signaling components present an embryonic lethality due to vascular defects. In patients, mutations in the TGF-h type I receptor ALK1 or in the accessory TGF-h receptor endoglin are linked to an autosomal dominant disorder of vascular dysplasia termed Hereditary Haemorrhagic Telangiectasia (HHT). It has puzzled researchers for years to explain the effects of TGFh being a stimulator and an inhibitor of angiogenesis in vitro and in vivo. Recently, a model has been proposed in which TGF-h by binding to the TGF-h type II receptor can activate two distinct type I receptors in endothelial cells (ECs), i.e., the EC-restricted ALK1 and the broadly expressed ALK-5, which have opposite effects on ECs behavior. ALK1 via Smad1/5 transcription factors stimulates EC proliferation and migration, whereas ALK5 via Smad2/3 inhibits EC proliferation and migration. Here, the new findings are presented concerning the molecular mechanisms that take place in ECs to precisely regulate and even switch between TGF-h-induced biological responses. In particular, the role of the accessory TGF-h receptor endoglin in the regulation of EC behavior is addressed and new insights are discussed concerning the possible mechanisms that are implicated in the development of HHT. D 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.