Acidic and basic fibroblast growth factors down-regulate collagen gene expression in keloid fibroblasts.
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.
Tan
E M
EM
Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Rouda
S
S
Greenbaum
S S
SS
Moore
J H
JH
Fox
J W
JW
Sollberg
S
S
D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D006909:Hydroxyproline / Q000096:biosynthesis; D007627:Keloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D003094:Collagen; D006909:Hydroxyproline