Cyclic AMP response element-binding protein prevents endothelial permeability increase through transcriptional controlling p190RhoGAP expression.

ABSTRACT: Increased endothelial permeability contributes to the morbidity and mortality associated with chronic inflammatory diseases, including acute lung injury. Cyclic AMP response element-binding protein (CREB) transcriptional factor induces genes that regulate inflammation and vascular remodeling. However, the role of CREB in regulating endothelial barrier function is unknown. Here, we demonstrate that CREB maintains basal endothelial barrier function and suppresses endothelial permeability increase by diverse agonists such as thrombin, lipopolysaccharide, histamine, and VEGF. We show that CREB transcriptionally controls the expression of p190RhoGAP-A, a GTPase-activating protein that inhibits small GTPase RhoA. Impairing CREB function using small interfering RNA or dominant-negative (dn)-CREB

SUBMITTER: Chava KR 

PROVIDER: S-EPMC3251234 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature