Igf-i increases bfgf induced mitogenesis and up-regulates fgf
receptor-1 in rabbit vascular smooth muscle cells.
Reape, Theresa J., Janos M. Kanczler, Jeremy P. T. Ward, and Chris R.
Thomas.
Department of Medicine, U.M.D.S., St. Thomas's Hospital, London SE1
7EH
APStracts 2:0414H, 1995.
Insulin-like Growth Factor-I (IGF-I) and basic Fibroblast Growth
Factor (bFGF) have both been implicated in the abnormal proliferation
of vascular smooth muscle cells (VSMC) which occurs after injury to
the arterial wall in vivo. We have investigated the effects of these
growth factors on proliferation of rabbit aortic smooth muscle cells
(RASMC) in vitro. IGF-I, in contrast to bFGF, is a weak mitogen for
RASMC. However, when IGF-I (10 ng/ml) was added in combination with
bFGF for 24 hours, the effect of the two growth factors on DNA
synthesis was synergistic at all concentrations tested (p <
0.001, compared to summed values of bFGF alone plus IGF-I alone) and
this synergy was also observed at the level of RASMC proliferation (p
< 0.001). Time course experiments indicated that although bFGF
was able to stimulate DNA synthesis after 16 hours, activity peaked
at 24 hours and a synergistic response with IGF-I was not observed
before 24 hours. Northern blot analysis demonstrated that IGF-I (10
ng/ml) could selectively up-regulate FGF receptor -1 (FGFR-1) mRNA
4.0 0.24 fold (p < 0.001) without a significant effect on FGFR-2
and this induction in FGFR-1 mRNA occurs in a time and dose dependent
manner. In addition, IGF-I increases FGFR-1 protein levels in RASMC
2.7 +/- 0.12 fold (p < 0.01), as demonstrated by Western
blotting and this up-regulation occurs before the peak in DNA
synthesis. These results suggest that IGF-I may be capable of
increasing the responsiveness of VSMC to bFGF through modulation of
FGFR-1.
Received 21 December 1994; accepted in final form 6 September
1995.
APS Manuscript Number H1124-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.