Sulfiredoxin-1 Inhibits PDGF-BB-Induced Vascular Smooth Muscle Cell Proliferation and Migration by Enhancing the Activation of Nrf2/ARE Signaling.

Abstract

Sulfiredoxin1 (Srxn1), an endogenous antioxidant protein, is involved in cardiovascular diseases. In this study, we aimed to investigate the role of Srxn1 in VSMCs and its molecular mechanism. The murine vascular smooth muscle cells MOVAS were treated with different doses of platelet-derived growth factor-BB (PDGF-BB); then, Srxn1 expression was detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. MTT and wound healing assay were used to examine the effect of Srxn1 on MOVAS cell proliferation and migration. Reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity in MOVAS cells were detected using corresponding commercial kits. Moreover, the expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2), and nuclear factor erythroid-2-related factor 2 (Nrf2) /antioxidant response element (ARE) signaling-related proteins was detected using western blot analysis. In our study, PDGF-BB dose-dependently increased Srxn1 expression in MOVAS cells, and Srxn1 expression was increased with time dependence in PDGF-BB-treated MOVAS cells. The knockdown of Srxn1 increased PDGF-BB-induced the proliferation, migration, ROS production, MDA level, and the protein expression of PCNA and MMP-2, as well as decreased SOD activity and the expression of Nrf2/ARE signaling-related proteins in PDGF-BB-stimulated MOVAS cells. However, the overexpression of Srxn1 showed the opposite results to those of knockdown of Srxn1. Moreover, the inhibitory effects of Srxn1 overexpression on PDGF-BB induced proliferation, migration, ROS production, and MDA level and the promotion of Srxn1 overexpression on PDGF-BB induced SOD activity were partially reversed by the knockdown of Nrf2. Srxn1 inhibited PDGF-BB-induced proliferation, migration, and oxidative stress through activating Nrf2/ARE signaling.