Effect of the platelet-derived growth factor antagonist trapidil on mesangial cell proliferation in rats.
Platelet-derived growth factor (PDGF) is known as a potent mediator in the proliferation of mesangial cells in culture and in mesangial proliferative nephritis. The present study was undertaken to evaluate the effect of trapidil, an antagonist of PDGF, on mesangial cell proliferation in culture and in anti-Thy-1.1 nephritis in rats. Trapidil significantly inhibited 3H-thymidine incorporation in the mesangial cells stimulated by PDGF BB and suppressed mesangial cell proliferation in culture in a dose-dependent manner. In anti-Thy-1.1 nephritis, a significant reduction in the number of total glomerular cells and also proliferating (proliferating cell nuclear antigen positive) cells was demonstrated on day 7 in the rats treated with trapidil as compared with controls. Although renal function expressed as blood urea nitrogen and creatinine levels did not differ between rats with and without trapidil treatment, the present results suggest a salutary effect of trapidil on mesangial cell proliferation. PDGF, therefore, could play an important role in mediating mesangial cell proliferation.
Futamura
A
A
2nd Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Izumino
K
K
Nakagawa
Y
Y
Takata
M
M
Inoue
H
H
Iida
H
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D015432:Glomerulonephritis, Membranoproliferative / Q000473:pathology; D007150:Immunohistochemistry; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014192:Trapidil / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D014192:Trapidil