Syndecan-4 regulates platelet-derived growth factor-mediated MAP kinase activation by altering intracellular reactive oxygen species

Abstract 

The cell adhesion receptor, syndecan-4, regulates cellular interactions with both the extracellular matrix and soluble ligands. Accumulating evidence also suggests that cell adhesion is involved in generating reactive oxygen species (ROS). Here, we investigated the role of syndecan-4 in regulating growth factor-induced ROS generation. Rat embryo fibroblasts (REFs) overexpressing syndecan-4 exhibited increased ROS levels compared to control cells. Expression of the non-phagocytic NADH oxidase component Nox1 was increased in syndecan-4-overexpressing REFs and syndecan-4-mediated ROS generation was diminished when levels of Nox1 were knocked-down with small inhibitory RNAs. In addition, syndecan-4 enhanced platelet-derived growth factor (PDGF)-induced MAP kinase activity in parallel with ROS generation. Collectively, these data suggest that syndecan-4 regulates PDGF-induced MAP kinase activation by altering ROS generation.

Keywords: Reactive oxygen species, Syndecan-4, MAP kinase, Platelet-derived growth factor

Abbreviations: DCF, fluorescent 2′,7′-dichlorofluorescein, ECM, extracellular matrix, FBS, fetal bovine serum, GST, glutathione-S-transferase, PDGF, platelet-derived growth factor, REF, rat embryo fibroblasts, ROS, reactive oxygen species, SDS, sodium dodecyl sulfate, SDS–PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis