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Am J Physiol Renal Physiol 266: F894-F900, 1994;
0363-6127/94 $5.00
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AJP - Renal Physiology, Vol 266, Issue 6 894-F900, Copyright © 1994 by American Physiological Society

ARTICLES

Endothelin modulates the mitogenic effect of PDGF on glomerular mesangial cells

M. Kohno, T. Horio, K. Yokokawa, K. Yasunari, N. Kurihara and T. Takeda
First Department of Internal Medicine, Osaka City University Medical School, Japan.

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.


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