The differential regulation and secretion of proteinases from fetal and neonatal fibroblasts by growth factors

Abstract

One of the major differences between fetal and adult wound repair is the unique ability of fetal wounds to heal without scarring. Since scar formation is a function of extracellular matrix deposition, the regulation of this component is fundamental in tissue remodeling. In this study, we have characterized the differences in the secretion of matrix-degrading proteases, namely urokinase plasminogen activator and gelatinase A and B, from fetal and neonatal fibroblasts. In addition, we examined the modulation of these protease levels by growth factors known to be important in wound repair. The results indicate that the secretion of these proteases differ significantly between the two cell types. The levels of urokinase plasminogen activator and its inhibitor were notably higher in media conditioned by neonatal fibroblasts in comparison to fetal samples. In contrast, the basal level of gelatinase A was comparable in both cell types, whilst the level of gelatinase B was elevated in the fetal fibroblasts. Transforming growth factor-β1 reduced the level of urokinase plasminogen activator and stimulated the secretion of plasminogen activator inhibitor-1 and progelatinase B in both neonatal and fetal fibroblasts. However, only progelatinase A and an activated form of gelatinase B were significantly elevated in fetal fibroblasts. In contrast, platelet-derived growth factor stimulated urokinase plasminogen activator, its inhibitor and both gelatinase A and B, an effect which was more apparent in fetal fibroblasts. This difference in protease regulation may be reflected in the differing rate and quality of tissue remodeling observed during adult vs fetal wound repair.