V. Stefanovic et al., EPIDERMAL GROWTH-FACTOR UP-REGULATES AMINOPEPTIDASE N AND 5'-NUCLEOTIDASE IN HUMAN GLOMERULAR MESANGIAL CELLS, Kidney & blood pressure research, 21(5), 1998, pp. 310-316
Because epidermal growth factor (EGF) is likely to be released in the
glomeruli during glomerular injury and mesangial cells possess specifi
c receptors for EGF we thought it to be of interest to examine whether
this growth factor could influence the expression of ectoenzymes in c
ultured human mesangial cells. EGF stimulated 5'-nucleotidase and amin
opeptidase N activities in intact human mesangial cells in a time- (24
-72 h) and dose-dependent (0.1-50 ng.ml(-1)) manner. Maximum stimulati
on represented 2.7- and 2-fold basal activities for 5'-nucleotidase an
d aminopeptidase N, respectively. EGF did not influence cyclic AMP pro
duction, and its effect on 5'-nucleotidase was additive to that of for
skolin or 8-bromo-cAMP. In contrast, genistein (10 mg.ml(-1)), an inhi
bitor of tyrosine kinase, prevented EGF-dependent stimulation of amino
peptidase N and 5'-nucleotidase, suggesting that protein phosphorylati
on was involved in the signaling mechanism. EGF stimulated specificall
y the latter two enzymes since it had no effect on other ectoenzymes i
ncluding alkaline phosphodiesterase I and Mg2+-ATPase activities. Thes
e 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 mesangi
al cell contractility and proliferation.