Protein Tyrosine Phosphatase PTPεM Negatively Regulates PDGF β-Receptor Signaling Induced by High Glucose and PDGF in Vascular Smooth Muscle Cells.

Vascular smooth muscle cell (VSMC) proliferation and migration and vascular endothelial cell (VEC) dysfunction are closely associated with the development of atherosclerosis. We previously demonstrated that protein tyrosine phosphatase e M (PTPeM) promotes VEC survival and migration. The present study investigates the biological functions of PTPeM in VSMCs and determines whether PTPeM is implicated in diabetes-accelerated atherosclerosis. We overexpressed wild-type and inactive PTPeM and an small interfering RNA (siRNA) of PTPeM by using an adenovirus vector to investigate the effects of PTPeM upon platelet-derived growth factor (PDGF)- and high glucose (HG)-induced responses of rat VSMCs in vitro. We found that PTPeM decreased PDGF-induced DNA synthesis and migration by reducing the phosphorylation level of the PDGF β-receptor (PDGFRβ) with subsequently suppressed H2O2 generation. The HG content in the medium generated H2O2, upregulated PDGFRβ expression and its tyrosine-phosphorylation, and elevated NAD...