REGULATION OF CHICK MUSCLE SATELLITE CELLS BY FIBROBLAST GROWTH-FACTORS - INTERACTION WITH INSULIN-LIKE GROWTH-FACTOR-I AND HEPARIN

This study describes the effect of acidic and basic fibroblast growth factor (FGF) on DNA synthesis in chick satellite cells in vitro and in teractions with insulin-like growth factor-I (ICE-I) and exogenous hep arin. Basic bFGF stimulated incorporation of [H-3]thymidine into DNA w ith a half-maximum concentration (ED(50)) of 3.23 +/- 0.33 pmol/l, mor e than 500-fold more potent than acidic FGF (ED(50) = 2.13 +/- 0.5 nmo l/l). Both bFGF and IGF-I allowed the cells to traverse the cell cycle with an approximate length of the G(1) phase of 12 h. When cells were incubated with bFGF and IGF-I together their effects on DNA synthesis were additive rather than synergistic throughout the full concentrati on range. Incubation of satellite cells with low concentrations of hep arin (ng/ml) to mimic the effect of endogenous heparan sulphate proteo glycan caused a small increase in DNA synthesis, whereas higher concen trations (mu g/ml) inhibited DNA synthesis in a dose-related manner. A low concentration of heparin increased DNA synthesis at the highest c oncentration of bFGF, but high doses of heparin inhibited the response to bFGF throughout the dose-response curve but without altering the E D(50). RNAse protection assay showed the expression of bFGF mRNA in pr oliferating cells which appeared to decrease on differentiation. The r esults suggest that aspects of neonatal muscle development are regulat ed by interactions between autocrine/paracrine growth factors such as IGF-I and bFGF, perhaps IGF-I derived from the circulation, and compon ents of the extracellular matrix. Concentrations of the matrix compone nts: may change throughout the neonatal period and into adulthood and have an important effect on the regulatory role played by the growth f actors.