Tan E M, Peltonen J
Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107.
Biochem J. 1991 Sep 15;278 ( Pt 3)(Pt 3):863-9. doi: 10.1042/bj2780863.
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.
瘢痕疙瘩是一种良性皮肤肿瘤，其特征是胶原蛋白过度沉积，特别是I型胶原蛋白。我们在此报告，在瘢痕疙瘩成纤维细胞培养物中，通过羟脯氨酸合成测量的胶原蛋白生物合成受到内皮细胞生长因子（ECGF）补充剂和肝素联合作用的显著抑制，抑制率为65%-80%。单独用ECGF孵育的成纤维细胞培养物与对照培养物相比，胶原蛋白合成也有可测量的约50%的下降。胶原蛋白合成的抑制与胶原蛋白基因表达的下调有关。mRNA-cDNA杂交体的定量测量显示，肝素和ECGF使I型胶原蛋白的基因表达下降超过80%。在单独用ECGF孵育的培养物中也观察到编码I型胶原蛋白的mRNA水平显著降低。结果表明，ECGF和肝素对胶原蛋白产生负调节作用，这种抑制主要是由于I型胶原蛋白基因的前α1（I）下调所致。此外，ECGF具有强大的抑制作用，肝素对这种抑制现象具有相加作用。
