THE DIFFERENTIAL REGULATION AND SECRETION OF PROTEINASES FROM FETAL AND NEONATAL FIBROBLASTS BY GROWTH-FACTORS

One of the major differences between fetal and adult wound repair is t he unique ability of fetal wounds to heal without scarring, Since scar formation is a function of extracellular matrix deposition, the regul ation of this component is fundamental in tissue remodeling. In this s tudy, we have characterized the differences in the secretion of matrix -degrading proteases, namely urokinase plasminogen activator and gelat inase A and B, from fetal and neonatal fibroblasts. In addition, we ex amined the modulation of these protease levels by growth factors known to be important in wound repair. The results indicate that the secret ion 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 compar ison to fetal samples. In contrast, the basal level of gelatinase A wa s comparable in both cell types, whilst the level of gelatinase B was elevated in the fetal fibroblasts. Transforming growth factor-pr reduc ed the level of urokinase plasminogen activator and stimulated the sec retion of plasminogen activator inhibitor-1 and progelatinase B in bot h neonatal and fetal fibroblasts. However, only progelatinase A and an activated form of gelatinase B were significantly elevated in fetal f ibroblasts. In contrast, platelet-derived growth factor stimulated uro kinase plasminogen activator, its inhibitor and both gelatinase A and B, an effect which was more apparent in fetal fibroblasts. This differ ence in protease regulation may be reflected in the differing rate and quality of tissue remodeling observed during adult vs fetal wound rep air. (C) 1997 Elsevier Science Ltd All rights reserved.