Regulation of Radixin Gene Expression in Pulmonary Endothelium by LPS and Cyclic Stretch

Abstract

Increased lung vascular permeability is a cardinal feature of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We previously have shown that the ezrin, radixin, and moesin (ERM) proteins differentially participate in agonists-induced endothelial cell (EC) barrier enhancement and hyperpermeability. In the present study we explore the regulation of radixin gene expression in lung inflammation by disease-associated genetic variants in the promoter and intronic regions of the RDX. A combination of genomic wide association study (GWAS), in silico analysis, and transfection of RDX promoter luciferase reporter were utilized. We analyzed RDX expression with Genomatix and Haploview for gene regulation and allele linkage disequilibrium (LD), respectively. Inflammatory stimuli LPS and 18% cyclic stretch (a model of mechanical lung injury) each time-dependently modulate both the protein expression of radixin and phosphorylation of ERMs. A GWAS study of African Americans identified one promoter (rs1...