Am. J. Respir. Cell Mol. Biol.,
Volume 20, Number 2, February, 1999 332-341
Peptide Growth Factors Regulate Insulin-Like Growth Factor Binding
Protein Production by Fetal Rat Lung Fibroblasts
Wayne A.
Price
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Insulin-like growth factor (IGF) binding proteins (IGFBPs) are expressed in fetal lung and may provide
important post-translational regulation of IGF-induced mitogenesis during lung organogenesis. Because of
the observation that growth factors can control cell growth through regulation of IGFBPs, we examined
IGFBP production by fetal lung fibroblasts following stimulation by peptide growth factors important for
fetal lung growth and development. Fetal lung fibroblasts were cultured in serum-free medium supplemented with various growth factors for up to 48 h, and IGFBPs in conditioned medium (CM) were analyzed by ligand blot and immunoblot techniques. Accumulation of CM IGFBP-3 was increased and
IGFBP-2 decreased by incubation with either keratinocyte growth factor (KGF) or epidermal growth factor (EGF). The effect of these factors on IGFBP-3 accumulation increased with time but the effects of
KGF on CM IGFBP-2 decreased over 48 h of incubation. CM IGFBP-4 was increased by 24 and 48 h incubation with basic fibroblast growth factor (bFGF; 2.1- and 2.7-fold increases at 24 and 48 h, respectively) and platelet-derived growth factor-BB (PDGF-BB; 4.2- and 14.9-fold increases at 24 and 48 h, respectively), and 48 h incubation with EGF (6.3-fold increase). In 48-h coincubation experiments, EGF in
combination with PDGF-BB or with bFGF, and bFGF in combination with PDGF-BB, resulted in IGFBP-4 accumulations twice that expected from a summation of the effects of either growth factor alone (IGFBP-4 increased 9.8-, 4.0-, and 1.8-fold by PDGF-BB, EGF, and bFGF, respectively; and 27.1-, 37.3-, and
13.0-fold by PDGF-BB plus EGF, PDGF-BB plus bFGF, and EGF plus bFGF, respectively). These results
suggest synergistic effects of these growth factors on IGFBP-4 accumulation in fetal lung fibroblast CM.
Because IGFBPs are known to regulate DNA synthesis, we speculate that peptide growth factors may alter
cell proliferation in fetal lung, in part through their effect on IGFBPs.
