Endothelin modulates the mitogenic effect of PDGF on glomerular mesangial cells.
We showed that two isoforms of platelet-derived growth factor (PDGF), AB and BB, stimulate the secretion of endothelin (ET)-1 from cultured rat mesangial cells. Then, we examined whether PDGF AB and BB stimulate mesangial cell proliferation through the modulation of the endogenous production of ET-1 in these cells. Mitogenesis experiments were assessed by tritiated thymidine incorporation into DNA under highest concentrations (10 ng/ml) of PDGF AB and BB in the presence and absence of anti-ET-1 antiserum or a selective A-type endothelin receptor (ETA receptor) antagonist, BQ-123. PDGF AB and BB potently stimulate thymidine incorporation. This stimulation was significantly attenuated in the presence of either anti-ET-1 antiserum or BQ-123 (10(-7)-10(-5)M). Results suggest that PDGF AB and BB stimulate ET-1 secretion in rat mesangial cells through PDGF beta-receptors, and endogenously produced ET-1 serves to modulate the mitogenic effect of PDGF AB and BB, probably via ETA receptors in these cells.
First Department of Internal Medicine, Osaka City University Medical School, Japan.
M
M
Kohno
T
T
Horio
K
K
Yokokawa
K
K
Yasunari
N
N
Kurihara
T
T
Takeda
D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D007106:Immune Sera / Q000276:immunology; D008934:Mitogens / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007106:Immune Sera; D008934:Mitogens; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)