Study On RTEF-1 Inhibiting Vascular Smooth Muscle Cell Senescence Through SRF/MYOCD Signal Pathway

[Objective] To explore the impact of Related Transcriptional Enhancer Factor(RTEF-1)on vascular smooth muscle cell(VSMC)senescence through SRF/MYOCD signal pathway.[Methods] Human Aortic Smooth Muscle Cell(HASMC)were pre-incubated with10g/L D-gal for 72 h.Cell senescence and RTEF-1 gene expression were checked.Full-length RTEF-1 gene sequence or small interfering RNA(si RNA)were transfected into HASMC.Cells were incubated with 10g/L D-gal for 72 h and cell phenotype transformation,proliferation,migration and the adhesion abilities as well as the actin cytoskeleton polymerization and expression of SRF and myocardin under different RTEF-1 gene expression background were dectected.Then cells in RTEF-1over-expression(o/e)group were treated with CCG-100602,an inhibitor of SRF-MYOCD signal pathway.Changes of above indicators were examined.[Results] Compared with control group,D-gal increased the number of SA-?-gal-positive cells(P < 0.05)and the MDA content(P < 0.01),decreased the SOD activity and proportion of cells in G0/G1 phase(P<0.01),while S-phase cells increased(P<0.01).In addition,the expression of RTEF-1 was reduced(P<0.01).RTEF-1 o/e inhibited the cell proliferation and migration(P < 0.05),increased the expression of ?-SMA(P<0.05)and calponin(P<0.01),decreased the expression of osteopontin?integrin ?3 and paxillin(P<0.01)and the expression of osteocalcin?integrin ?5 and vinculin(P<0.05)as well as the ratio of G-actin/F-actin(P<0.01).Moreover,RTEF-1 o/e increased the expression of SRF and MYOCD(P<0.01).On the other hand,transfection of RTEF-1 si RNA has the opposite effects.CCG-100602 treatment reversed the above changes partly.[Conclusion] D-gal induced VSMC senescent and expression of RTEF-1 was reduced in senescent VSMC.RTEF-1 prevented phenotype switching of the senescent VSMC from differentiated contractile phenotypes into synthetic phenotype or osteogenic phenotype.It also inhibited cell proliferation,migration and adhesion,promoted actin cytoskeleton polymerization and cell contractility of senescent VSMC.SRF/MYOCD signaling pathway played a role in the effects of RTEF-1 on senescent VSMC.