Journal of cellular physiology
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Urocortin (Ucn1), a member of corticotrophin-releasing hormone (CRH) family, has been reported to be upregulated in inflammatory diseases and function as an autocrine or paracrine inflammatory mediator. Growing evidence shows that Ucn1 increases the endothelial permeability in inflammatory conditions; however, the detailed mechanisms are not clear. In the present study, we investigated the mechanisms of increased endothelial permeability by Ucn1 in human umbilical vein endothelial cells (HUVECs) exposed to lipopolysaccharide (LPS). ⋯ Increased β-catenin translocated into the nucleus and subsequently bound to TCF/LEF site, contributing to the elevated expression of vascular endothelial growth factor (VEGF). The above effects of Ucn1 were completely reversed by CRHR(2) receptor blocker, antisauvagine-30. Taken together, our data suggest that Ucn1 increase LPS-induced endothelial permeability by disrupting the VE-cadherin-β-catenin complex via activation of CRHR(2) and PKD-HSP27 signaling pathway.