Expression of human collagenase-3 (MMP-13) by fetal skin fibroblasts is induced by transforming growth factor beta via p38 mitogen-activated protein kinase.
: Ravanti L., Toriseva M., Penttinen R., Crombleholme T., Foschi M., Han J., Kähäri V.
: 2001
: FASEB Journal
: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
: 15
: 6
: 1098
: 1100
: 0892-6638
: http://api.elsevier.com/content/abstract/scopus_id:0035318547
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
β
1 (TGF-
β
1) and
TGF-
β
3, whereas MMP-13 expression was not detected in neonatal skin fibroblasts. Treatment
of fetal skin fibroblasts with TGF-
β
1 potently activated p38 mitogen-activated protein kinase
(MAPK). Induction of MMP-13 expression by TGF-
β
1 was blocked by p38 MAPK inhibitor
SB203580, and by adenovirally delivered dominant negative form of p38
α
. 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.