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.

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