Jianjie Wang
Missouri State University, USA
Title: Inflammatory role of nucleotide P2Y2 receptor: Vascular hyperpermeability
Biography
Biography: Jianjie Wang
Abstract
Extracellular nucleotides and their cell surface receptors have emerged as key players in inflammation. Hyperpermeability is a hallmark of inflammation and leads to vascular leak resulting in pulmonary edema that often occurs in the intensive care unit (ICU). To date, there is no specific pharmaceutical treatment for edema by a strategy of anti-vascular leakage except expulsion of excess fluid in the form of urine by diuretic drugs. Recently emerging evidence demonstrates nucleotide P2Y2 receptors play important roles in vascular inflammation, including arterial neointimal hyperplasia, increased vascular cell adhesion molecule-1 expression. My in vivo studies revealed that nucleotide P2Y2 receptor activation induced transient 5-fold increase in venular permeability to albumin (Ps) from baseline in wild type (WT) mice, but not in P2Y2 R knockout (P2Y2 R KO) mice. The P2Y2 R signaling-dependent hyperpermeability was mediated by focal adhesion kinase (FAK). Activation P2Y2 R induced phosphorylation of FAK at tyrosine-397 in origin-matched primary cultured murine microvascular endothelial cells. VE-cadherin, a key molecule of the adherens junction present at endothelial cell-cell junctions, increased activity in response to P2Y2 R agonist, UTP, implicating the paracellular pathway contributing to hyperpermeability. Taken together, the findings support nucleotide P2Y2 R play important role in microvascular leak.