PHYSIOLOGICAL AND BIOCHEMICAL RESPONSE OF GLOMERULAR EPITHELIAL-CELLSTO EXOGENOUS EPIDERMAL GROWTH-FACTOR

Epidermal growth factor (EGF) is a growth-promoting cytokine which act s in a paracrine and autocrine fashion on epithelial cells of various tissues. Although previously demonstrated, we have now confirmed the p resence of EGF receptors in cultured glomerular epithelial cells (GEC) using radioligand binding studies. Further, the biochemical consequen ces of EGF receptor activation in this cell type were investigated. In the presence of exogenous EGF, attachment of GEC to plastic was enhan ced in a dose-dependent (0.62-10 ng/ml range) manner. At 10 ng/ml of E GF, cell attachment was 5 times higher than in controls. After attachm ent, there was a 3-fold increase in cell proliferation rate in the pre sence of 10 ng/ml of EGF. Cells which multiplied and reached confluenc y in the presence of EGF were 80% larger in volume than in controls. I n the presence of EGF, a 70% maximal increase in de novo protein synth etic activity as tested by H-3-leucine incorporation was observed in t he dose range of 0.62-10 ng/ml. Further, a dose-dependent increase in extracellular type IV collagenase (gelatinase) as well as in intracell ular cathepsins B and D (150 and 260% of control, respectively) activi ties were noted. It is concluded that GEC respond to exogenous EGF by increasing their protein synthetic rate as well as their catabolic rat e, thus resulting in enhanced turnover of macromolecules.