Xeroderma Pigmentosum Group D (XPD) Inhibits the Proliferation Cycle of Vascular Smooth Muscle Cell (VSMC) by Activating Glycogen Synthase Kinase 3β (GSK3β)

BACKGROUND: VSMC proliferation plays a key role in atherosclerosis, but the role of XPD in VSMC proliferation remains unknown. We investigated the expression of XPD, which is involved in cell cycle regulation, and its role in VSMC proliferation response to atherogenic stimuli. MATERIAL/METHODS: Human umbilical vein VSMCs were transfected with recombinant plasmid pEGFP-N2/XPD and pEGFP-N2 and incubated with PDGF-BB in vitro. Cell viability was determined by MTT assay. The expressions of XPD, GSK3β, p-GSK3β, CDK4, and cyclin D1 protein were detected by Western blot analysis. Cell cycle was examined by flow cytometry. RESULTS: PDGF inhibited the expression of XPD in VSMCs and promoted VSMC proliferation. Overexpression of XPD significantly augmented cell cycle arrest, and attenuated protein expression levels of CDK4 and cyclin D1 in VSMCs. XPD overexpression suppressed the effects of PDGF-BB in promoting G1/S transition and accelerating protein expression levels of CDK4 and cyclin D1. XPD diminished the phosphorylation of GSK3β, and SB216763 inhibited the reduction effect of XPD on CDK4 and cyclin D1. CONCLUSIONS: XPD induces VSMC cell cycle arrest, and the activation of GSK3β plays a crucial role in inhibitory effect of XPD on VSMC proliferation.