Expression of human collagenase-3 (MMP-13) by fetal skin fibroblasts is induced by transforming growth factor beta via p38 mitogen-activated protein kinase.

Abstract

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