Rapid induction and translocation of Egr-1 in response to mechanical strain in vascular smooth muscle cells

The effect of mechanical strain on transcription and expression of the imme diate-early genes, early growth response gene-1 (Egr-1), c-jun, and c-fos, was investigated in neonatal rat aortic vascular smooth muscle (VSM) cells. Cells grown on silicone elastomer plates were subjected to cyclic mechanic al strain (1 Hz) at various durations and magnitudes. Egr-1 mRNA increased rapidly in response to cyclic strain, reached a maximum of 10-fold after 30 minutes, and returned to baseline after 4 hours. c-jun exhibited a similar pattern, whereas c-fos mRNA expression was unaffected by strain. Cyclohexi mide prolonged the increase in Egr-1 and c-jun mRNA and caused superinducti on of both. The threshold level of continuous cyclic strain needed to induc e expression was 5% for Egr-1 and c-jun. Even a single cycle of mechanical strain that lasted 1 second was sufficient to induce Egr-1 and c-jun mRNA, Strain also increased expression of a transiently transfected Egr-1 promote r-reporter construct. The effect of varying extracellular matrices on strai n-induced Egr-1 and c-jun mRNA was examined. In contrast to collagen type 1 - and pronectin-coated plates, strain did not significantly alter expressio n of Egr-1 and c-jun was less induced on laminin-coated plates. On collagen type 1, strain increased Egr-1 protein levels by 2.1-fold at 60 minutes. I mmunofluorescence microscopy revealed translocation of Egr-1 to the nucleus in response to strain. These observations indicate that Egr-1 expression a nd translocation are sensitive to mechanical perturbation of the cell. c-ju n is also induced by strain, but c-fos is not. The signal for this inductio n may involve specific cell-matrix interactions.