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Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema by altering Tie2 expression.


ABSTRACT: Tight regulation of vascular permeability is necessary for normal development and deregulated vascular barrier function contributes to the pathogenesis of various diseases, including acute respiratory distress syndrome, cancer and inflammation. The angiopoietin (Ang)-Tie2 pathway is known to control vascular permeability. However, the mechanism by which the expression of Tie2 is regulated to control vascular permeability has not been fully elucidated. Here we show that transcription factor Twist1 modulates pulmonary vascular leakage by altering the expression of Tie2 in a context-dependent way. Twist1 knockdown in cultured human lung microvascular endothelial cells decreases Tie2 expression and phosphorylation and increases RhoA activity, which disrupts cell-cell junctional integrity and i

SUBMITTER: Mammoto T 

PROVIDER: S-EPMC3759405 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature