Eicosapentaenoic acid inhibits mitogen-induced endothelin-1 production and DNA synthesis in cultured bovine mesangial cells

The present study was designed to examine whether eicosapentaenoic acid (EPA) inhibits the production of basal or stimulated endothelin (ET)-1 by platelet-derived growth factor (PDGF)-BB or epidermal growth factor (EGF), and DNA synthesis in cultured bovine mesangial cells. PDGF-BB and EGF stimulated ET-1 secretion in a dose-dependent fashion in these cells. EPA(10-100 mu M) exhibited dose-related inhibition of PDGF-BB- and EGF-stimulated ET-1 secretion. EPA had no inhibitory effects on basal ET-1 secretion in these cells. Moreover, 50 mu M EPA significantly attenuated PDGF-BB-and EGF-stimulated [H-3]thymidine incorporation into mesangial cells. Receptor-binding experiments showed that EPA competitively inhibited I-125-PDGF-BB or I-125-EGF binding to mesangial cell surface receptors. Scatchard analysis for PDGF-BB receptor or EGF receptor revealed a linear regression fit and one binding site. Pretreatment with 50 mu M EPA suppressed the number of maximum binding sites, but did not affect the K-d values. These results indicate that EPA potentially inhibits mesangial cell ET-I production, when stimulated by PDGF-BB or EGF. This inhibitory effect of EPA could be related to the attenuation of mesangial cell proliferation via inhibition of the binding of PDGF-BB or EGF to their receptors due to alteration of the physicochemical characteristics of the cell membrane.