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VE-cadherin is a critical endothelial regulator of TGF-beta signalling : phd degree in moleculare medicine

Rudini, Noemi <1979- >

Tesi o dissertazioni - 2009

ABSTRACT Transforming growth factor-ß (TGF-ß) is a cytokine that regulates proliferation and migration of many cell types. In endothelial cells (ECs), TGF-ß mediates its cellular effects through serine/threonine kinase receptors: a TGF-ß type II receptor (TßRII) and two TGF-ß type I receptors (ALK1 and ALK5). Ligand-dependent assembly of these receptors results in activation of the Smad proteins which regulate target gene transcription. Endothelial adherens junctions (AJs) are junctional protein structures that regulate vascular homeostasis. Vascular endothelial cadherin (VE-cadherin) is the main component of endothelial AJs that mediates cell-to-cell homophilic adhesion and transfers intracellular signals to promote the steady state of the endothelium. The notion that TGF-ß receptors knockout (KO) mice phenotype resembles that of VE-cadherin KO mice prompted us to investigate a crosstalk between TGF-ß and AJ pathways in ECs. We report that VE-cadherin expression and junctional clustering are required for optimal TGF-ß signaling in ECs [...]
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