Epidermal Growth Factor Upregulates Aminopeptidase N and 5′–Nucleotidase in Human Glomerular Mesangial Cells

Because epidermal growth factor (EGF) is likely to be released in the glomeruli during glomerular injury and mesangial cells possess specific receptors for EGF, we thought it to be of interest to examine whether this growth factor could influence the expression of ectoenzymes in cultured human mesangial cells. EGF stimulated 5′–nucleotidase and aminopeptidase N activities in intact human mesangial cells in a time– (24–72 h) and dose–dependent (0.1–50 ng·ml^–1) manner. Maximum stimulation represented 2.7– and 2–fold basal activities for 5′–nucleotidase and aminopeptidase N, respectively. EGF did not influence cyclic AMP production, and its effect on 5′–nucleotidase was additive to that of forskolin or 8–bromo–cAMP. In contrast, genistein (10 mg·ml^–1), an inhibitor of tyrosine kinase, prevented EGF–dependent stimulation of aminopeptidase N and 5′–nucleotidase, suggesting that protein phosphorylation was involved in the signaling mechanism. EGF stimulated specifically the latter two enzymes since it had no effect on other ectoenzymes including alkaline phosphodiesterase I and Mg²⁺–ATPase activities. These results demonstrate that EGF, via the control of 5′–nucleotidase and aminopeptidase N, which are implied in adenosine formation and peptide processing, respectively, could play a role in human cultured mesangial cell contractility and proliferation.