The effects of acidic and basic
fibroblast growth factors (FGFs) on
collagen expression by
keloid fibroblasts were examined in the absence and presence of
heparin.
Collagen biosynthesis and gene expression of
type I collagen were down-regulated by the FGFs in the presence of
heparin. Acidic FGF, in a concentration range of 0.4 to 50 ng/ml, had little or no effect on
collagen synthesis after a 4-day incubation. However, in the presence of
heparin (100 micrograms/ml) acidic FGF, in concentrations ranging from 2 to 50 ng/ml, decreased [3H]
hydroxyproline synthesis by 44 to 68%, compared with untreated control cultures. Total [3H]
hydroxyproline synthesis was similar between control and
heparin-treated cultures. Basic FGF (2.0 to 50 ng/ml) was effective in suppressing [3H]
hydroxyproline synthesis by 50 to 90% after a 4-day incubation without
heparin in
keloid and normal fibroblast cultures. The steady-state levels of
type I collagen messenger RNA were significantly decreased by acidic FGF in the presence of
heparin, as well as by basic FGF without
heparin. The data suggest that the FGFs are effective in down-regulating excess
collagen production by
keloid fibroblasts and that this inhibitory effect is apparently associated with pretranslational events. Moreover, acidic FGF is apparently dependent on
heparin, whereas basic FGF is not, for potentiation of the down-regulatory effects of the FGFs.