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 microM) 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 microM EPA significantly attenuated PDGF-BB- and EGF-stimulated [3H]thymidine incorporation into mesangial cells. Receptor-binding experiments showed that EPA competitively inhibited 125I-PDGF-BB or 125I-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 microM EPA suppressed the number of maximum binding sites, but did not affect the Kd values. These results indicate that EPA potentially inhibits mesangial cell ET-1 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.
Nitta
K
K
Department of Medicine, Tokyo Women's Medical College, Japan.
Uchida
K
K
Tsutsui
T
T
Honda
K
K
Kawashima
A
A
Yumura
W
W
Nihei
H
H
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000077214:Becaplermin; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008934:Mitogens / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D000925:Anticoagulants; D019332:Endothelin-1; D007457:Iodine Radioisotopes; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D004247:DNA; D015118:Eicosapentaenoic Acid