Expression of human collagenase-3 (MMP-13) by fetal skin fibroblasts is induced by transforming growth factor-beta via p38 mitogen-activated protein kinase
Han, J. H.
Kahari, V. M.
- 生命科学－已发表论文 
Human collagenase-3 (MMP-13) is characterized by wide substrate specificity and limited tissue specific expression. We have previously noted that human collagenase-3 (MMP-13) is expressed by gingival fibroblasts in culture and during gingival wound repair characterized by minimal scarring. Here we show that human MMP-13 is expressed by dermal fibroblasts during early wound repair in fetal skin grafted on SCID mice. The expression of MMP-13 by fetal skin fibroblasts in monolayer culture was enhanced by transforming growth factor b1 (TGF-beta 1) and TGF-beta 3, whereas MMP-13 expression was not detected in neonatal skin fibroblasts. Treatment of fetal skin fibroblasts with TGF-beta 1 potently activated p38 mitogen-activated protein kinase (MAPK). Induction of MMP-13 expression by TGF-beta 1 was blocked by p38 MAPK inhibitor SB203580, and by adenovirally delivered dominant negative form of p38 alpha. These observations demonstrate a remarkable difference in the regulation of collagenolytic capacity between fetal and neonatal skin fibroblasts, which suggests a role for MMP-13 in rapid turnover of collagenous matrix during repair of fetal cutaneous wounds, which heal without scar.