AJP - Cell Physiology, Vol 256, Issue 4 C886-C892, Copyright © 1989 by American Physiological Society
Mitogenesis by serum and PDGF is independent of PI degradation and PKC in VSMC
M. Kihara, P. J. Robinson, S. H. Buck and R. C. Dage
Merrell Dow Research Institute, Cincinnati 45215.
Capacities of serum, platelet-derived growth factor (PDGF), and fibroblast
growth factor (FGF) on phosphatidylinositol (PI) degradation and cell
growth were compared in cultured vascular smooth muscle cells (VSMC) from
rat aorta. The role of protein kinase C (PKC) in growth control was also
evaluated using polymixin B, a selective inhibitor of PKC. Both dialyzed
and nondialyzed fetal bovine serum (FBS) in concentrations from 2 to 20%
stimulated [3H]thymidine incorporation into DNA and cell growth without
producing corresponding increases in PI turnover. Moreover, both PDGF
(40-160 ng/ml) and FGF (6.25-150 ng/ml) also stimulated mitogenesis, but
PDGF was more effective although less potent. Mitogenic amounts of PDGF did
not stimulate PI turnover, whereas a maximally mitogenic amount of FGF (50
ng/ml) did produce a slight increase. Polymixin B inhibited PKC activity
(IC50, 32 microM) from these cells but failed to suppress DNA synthesis
produced by 10% FBS or PDGF (50 ng/ml). However, it did suppress that by
FGF (50 ng/ml). Angiotensin II (10(-11)-10(-7) M) and phorbol
12,13-dibutyrate (PDB, 1-20 nM) were not mitogenic in the presence or
absence of insulin (10 micrograms/ml) or the calcium ionophore A23187
(0.25-4 microM), under serum-free conditions. Instead, PDB inhibited
mitogenesis of cells maintained under 0.2% FBS or stimulated with insulin
(10 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
