The cellular repressor of E1A-stimulated genes induces differentiation and migration of human vascular smooth muscle cells

In order to study the effect of the cellular repressor of E1A-stimulated genes (CREG) on differentiation and migration of human vascular smooth muscle cells (VSMCs)-HlTASY, the full length human sense and antisense-CREG cDNA retroviral vectors, pLNCX(2)(+)/CREG and pLXSN(-)/CREG, were constructed. Western blot and immunoflourescence analysis showed that the expression of CREG and SM alpha -actin increased in HITASY after infection with pLNCX(2)(+) /CREG. The migration of HITASY infected with pLNCX(2)(+)/CREG obviously enhanced compared with that of normal HITASY and pLXSN(-)/CREG cells showed by scrape-wounding and time-lapse analysis. Moreover, CREG over-expression increased the secretion of MMPs in HITASY tested by Western blot. Gelatin SDS-PAGE zymography analysis revealed that the activities of MMPs also increased in HITASY infected with pLNCX2(+)/CREG. On the other hand, the opposite effects were observed when CREG expression decreased by using antisense pLXSN(-)/CREG. These results suggest that CREG may be able to induce the VSMCs differetiation and promote the VSMCs migration in the meantime.