Regulation of chick muscle satellite cells by fibroblast growth factors: interaction with insulin-like growth factor-I and heparin

Abstract

This study describes the effect of acidic and basic fibroblast growth factor (FGF) on DNA synthesis in chick satellite cells in vitro and interactions with insulin-like growth factor-I (IGF-I) and exogenous heparin. Basic bFGF stimulated incorporation of [3H]thymidine into DNA with a half-maximum concentration (ED50) of 3.23 +/- 0.33 pmol/l, more than 500-fold more potent than acidic FGF (ED50 = 2.13 +/- 0.5 nmol/l). Both bFGF and IGF-I allowed the cells to traverse the cell cycle with an approximate length of the G1 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 concentration range. Incubation of satellite cells with low concentrations of heparin (ng/ml) to mimic the effect of endogenous heparan sulphate proteoglycan caused a small increase in DNA synthesis, whereas higher concentrations (microgram/ml) inhibited DNA synthesis in a dose-related manner. A low concentration of heparin increased DNA synthesis at the highest concentration of bFGF, but high doses of heparin inhibited the response to bFGF throughout the dose-response curve but without altering the ED50. RNAse protection assay showed the expression of bFGF mRNA in proliferating cells which appeared to decrease on differentiation. The results suggest that aspects of neonatal muscle development are regulated by interactions between autocrine/paracrine growth factors such as IGF-I and bFGF, perhaps IGF-I derived from the circulation, and components of the extracellular matrix. Concentrations of the matrix components may change throughout the neonatal period and into adulthood and have an important effect on the regulatory role played by the growth factors.