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American Journal of Pathology, Vol 136, 557-563, Copyright © 1990 by American Society for Investigative Pathology

REGULAR ARTICLES

Reversal of inhibition of rat glomerular epithelial cell growth by growth factors

S Adler and B Eng
Department of Medicine, New York Medical College, Valhalla.

The ability of several growth factors to reverse heparin-induced inhibition of rat glomerular epithelial cell (GEC) growth and the mechanism of growth inhibition were explored in vitro. Insulin-like growth factor-1, rat multiplication-stimulating activity, and platelet- derived growth factor had no effect on proliferation of cultured GEC exposed to heparin (100 micrograms/ml). Epidermal growth factor (EGF) partially reversed heparin-induced growth inhibition in a dose- dependent fashion with a maximum effect seen at 1 ng/ml. No additive effect was seen with combinations of EGF and the other growth factors assayed. A decrease in EGF-stimulated incorporation of 3H-thymidine by GEC was seen with as little as 2 hours of heparin exposure and persisted for up to 48 hours. Heparin consistently increased binding of 125I-EGF to GEC with a significant increase apparent after 2 hours of exposure and a further increase with a 24-hour exposure. Increased EGF binding to heparin-treated cells was due to a significant increase in the association constant of EGF and its receptor with no effect on receptor number. Interactions between GEC and heparinlike glycosaminoglycans in the glomerular basement membrane may play a role in the regulation of GEC proliferation in normal and diseased states.

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