TGF-beta signaling in vascular biology and dysfunction.

Marie-José Goumans, Zhen Liu, Peter ten Dijke

Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

Cell research 2009 Jan

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Transforming growth factor (TGF)-beta family members are multifunctional cytokines that elicit their effects on cells, including endothelial and mural cells, via specific type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. Knock-out mouse models for TGF-beta family signaling pathway components have revealed their critical importance in proper yolk sac angiogenesis. Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular syndromes such as hereditary hemorrhagic telangiectasia, primary pulmonary hypertension and Marfan syndrome. In this review, we present recent advances in our understanding of the role of TGF-beta receptor signaling in vascular biology and disease, and discuss how this may be applied for therapy.