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 aci d (EPA) inhibits the production of basal or stimulated endothelin (ET) -1 by platelet-derived growth factor (PDGF)-BB or epidermal growth fac tor (EGF), and DNA synthesis in cultured bovine mesangial cells. PDGF- BB and EGF stimulated ET-1 secretion in a dose-dependent fashion in th ese cells. EPA(10-100 mu M) exhibited dose-related inhibition of PDGF- BB- and EGF-stimulated ET-1 secretion. EPA had no inhibitory effects o n basal ET-1 secretion in these cells. Moreover, 50 mu M EPA significa ntly attenuated PDGF-BB-and EGF-stimulated [H-3]thymidine incorporatio n into mesangial cells. Receptor-binding experiments showed that EPA c ompetitively inhibited I-125-PDGF-BB or I-125-EGF binding to mesangial cell surface receptors. Scatchard analysis for PDGF-BB receptor or EG F receptor revealed a linear regression fit and one binding site. Pret reatment with 50 mu M EPA suppressed the number of maximum binding sit es, 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 t he attenuation of mesangial cell proliferation via inhibition of the b inding of PDGF-BB or EGF to their receptors due to alteration of the p hysicochemical characteristics of the cell membrane.