Endothelial cell growth factor and heparin regulate collagen gene expression in keloid fibroblasts.
Keloids are benign cutaneous tumours characterized by excess deposition of collagen, specifically type I collagen. We report here that collagen biosynthesis, as measured by hydroxyproline synthesis, was markedly inhibited by 65-80% by the combination of endothelial cell growth factor (ECGF) supplement and heparin in keloid fibroblast cultures. Fibroblast cultures that were incubated with ECGF alone also demonstrated a measurable decrease of approx. 50% in collagen synthesis compared with control cultures. The inhibition of collagen synthesis was related to the down-regulation of collagen gene expression. Quantitative measurements of mRNA-cDNA hybrids revealed that the gene expression of collagen type I was decreased by more than 80% by heparin and ECGF. Markedly diminished levels of mRNA encoding collagen type I were also observed in cultures incubated with ECGF alone. The results show that ECGF and heparin elicit a negative regulatory effect on collagen production, and that this inhibition is due largely to the down-regulation of the pro-alpha 1(I) of type I collagen gene. Furthermore, ECGF has a potent suppressive effect, and heparin provides an additive effect to this inhibitory phenomenon.
Tan
E M
EM
Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107.
Peltonen
J
J
D000328:Adult; D015152:Blotting, Northern; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D015342:DNA Probes; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D006909:Hydroxyproline / Q000096:biosynthesis; D007627:Keloid / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D015342:DNA Probes; D016228:Endothelial Growth Factors; D012333:RNA, Messenger; D006493:Heparin; D003094:Collagen; D006909:Hydroxyproline