Human recombinant insulin-like growth factor I and -II stimulate the expression of basic fibroblast growth factor but suppress the division of bovine coronary smooth muscle cells

Abstract Insulin-like growth factor I and II (IGF-I and -II) — two 7.65- and 7.47-kDa polypeptides belonging to the somatomedine family — are regular constituents of human blood plasma. Both factors exert mitogenic activity on a variety of cell types including arterial smooth muscle cells. In the present study, the effect of IGF-I and -II on cultured bovine coronary smooth muscle cells (cSMC) was assessed. Human recombinant IGF-I and IGF-II added to cSMC cultured in a medium containing 10% fetal bovine serum (FBS) decreased the cell number and [ 3 H]thymidine incorporation in a dose dependent fashion up to 40% and 43% compared to control cells (100%). At the same time, the expression of basic fibroblast growth factor (bFGF) increased from 60 pg/5 × 10 4 cells (control) to 75 (IGF-I) and 113 pg5 x 104 cells (IGF-II). In parallel with enhanced bFGF expression, the bFGF receptor content per cell and the [ 35 S]sulfate incorporation into extracellular and cell-associated proteoglycans also increased under the influence of IGF-I and -II. In contrast, with low serum concentration (0.1% FBS) the addition of IGF-I and -II to bovine cSMC cultures resulted in a slight increase in cell number, protein content and [ 3 H]thymidine incorporation as described in previous studies. These results suggest that the mitogenic activity of IGF-I and -II towards coronary smooth muscle cells depends on culture conditions. In the presence of 10% fetal bovine serum that mimics in vivo conditions. IGF-I and -II did not necessarily act as mitogenic factors but inhibited the proliferation of cSMC in vitro possibly by modulating and antagonizing the action of other growth factors. Irrespective of the inhibition of cell division, the cellular bFGF, the bFGF receptor and the bFGF activity-related proteoheparan sulfate were overexpressed under the influence of IGF.