Egr-1 is Activated in Endothelial Cells Exposed to Fluid Shear Stress and Interacts With a Novel Shear-Stress-Response Element in the PDGF A-Chain Promoter

摘要: Abstract Exposure of vascular endothelial cells to fluid mechanical forces can modulate the expression many genes involved in physiology and pathophysiology. Here, we report that platelet-derived growth factor (PDGF) A-chain gene is induced at level transcription cultured bovine aortic exposed a physiologic steady laminar shear stress (10 dyn/cm2). 5′ Deletion analysis human PDGF-A promoter revealed GC-rich region near TATA box was required for shear-inducible reporter expression. This element conferred inducibility onto heterologous promoter-reporter construct otherwise unresponsive stress. The induction by preceded rapid transient immediate-early gene, egr-1 , which binds sequences. Gel shift studies indicated shear-induced Egr-1 bound proximal specific time-dependent manner, displacing Sp1 from their overlapping recognition elements. Overlapping consensus binding sites also appear promoters several other genes, including transforming factor-β1 tissue factor, whose modulated These findings define site as shear-stress-responsive suggest shear-stimulated may be unifying theme various biomechanical forces.