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TGF-beta receptor function in the endothelium.

Franck Lebrin·Martine Deckers·Philippe Bertolino·Peter Ten Dijke
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Abstract

Genetic studies in mice and humans have revealed the pivotal role of transforming growth factor-beta (TGF-beta) signaling during angiogenesis. Mice deficient for various TGF-beta signaling components present an embryonic lethality due to vascular defects. In patients, mutations in the TGF-beta type I receptor ALK1 or in the accessory TGF-beta 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 TGF-beta being a stimulator and an inhibitor of angiogenesis in vitro and in vivo. Recently, a model has been proposed in which TGF-beta by binding to the TGF-beta 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-beta-induced biological responses. In particular, the role of the accessory TGF-beta 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.

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AnimalsEndothelium, VascularHumansMiceNeovascularization, PhysiologicReceptors, Transforming Growth Factor betaSignal TransductionTelangiectasia, Hereditary HemorrhagicTransforming Growth Factor betaJournal ArticleResearch Support, Non-U.S. Gov'tReview

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Franck Lebrin, Martine Deckers, Philippe Bertolino, Peter Ten Dijke. 2005-02-15. TGF-beta receptor function in the endothelium.. https://doi.org/10.1016/j.cardiores.2004.10.036

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