Physiological and biochemical response of glomerular epithelial cells to exogenous epidermal growth factor

Epidermal growth factor (EGF) is a growth-promoting cytokine which acts in a paracrine and autocrine fashion on epithelial cells of various tissues. Although previously demonstrated, we have now confirmed the presence of EGF receptors in cultured glomerular epithelial cells (GEC) using radioligand binding studies. Further, the biochemical consequences of EGF receptor activation in this cell type were investigated. In the presence of exogenous EGF, attachment of GEC to plastic was enhanced in a dose-dependent (0.62-10 ng/ml range) manner. At 10 ng/ml of EGF, cell attachment was 5 times higher than in controls. After attachment, there was a 3-fold increase in cell proliferation rate in the presence of 10 ng/ml of EGF. Cells which multiplied and reached confluency in the presence of EGF were 80% larger in volume than in controls. In the presence of EGF, a 70% maximal increase in de novo protein synthetic activity as tested by 3H-leucine incorporation was observed in the dose range of 0.62-10 ng/ml. Further, a dose-dependent increase in extracellular type IV collagenase (gelatinase) as well as in intracellular cathepsins B and D (150 and 260% of control, respectively) activities were noted. It is concluded that GEC respond to exogenous EGF by increasing their protein synthetic rate as well as their catabolic rate, thus resulting in enhanced turnover of macromolecules.