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	Transforming growth factor-beta induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase
	Ravanti, L. ; Hakkinen, L. ; Larjava, H. ; Saarialho-Kere, U. ; Foschi, M. ; Han, J. H. ; Kahari, V. M. ; Han JH(韩家淮)
	1999
关键词	SQUAMOUS-CELL CARCINOMAS MATRIX METALLOPROTEINASE-13 TISSUE INHIBITOR GENE-EXPRESSION MESSENGER-RNA BREAST CARCINOMAS MAP KINASE I COLLAGEN MMP-13 KERATINOCYTES
英文摘要	Human collagenase-3 (matrix metalloproteinase 13 (MMP-13)) is characterized by exceptionally wide substrate specificity and restricted tissue specific expression. Human skin fibroblasts in culture express MMP-13 only when they are in three-dimensional collagen (Ravanti, L., Heino, J., Lopez-Otin, C,, and Kahari. V.-M. (1999) J. Biol. Chem. 274, 2446-2455). Here we show that MMP-13 is expressed by fibroblasts during normal human gingival wound repair. Expression of MMP-13 by human gingival fibroblasts cultured in monolayer or in collagen gel was induced by transforming growth factor-beta 1 (TGF-beta 1). Treatment of gingival fibroblasts with TGF-beta 1 activated two distinct mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2) in 15 min and p38 MAPK in 1 and 2 h. Induction of MMP-13 expression by TGF-beta 1 was blocked by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a selective inhibitor of ERK1/2 activation. Adenovirus-mediated expression of dominant negative p38 alpha and c-Jun potently inhibited induction of MMP-13 expression in gingival fibroblasts by TGF-beta 1. Infection of gingival fibroblasts with adenovirus for constitutively active MEK1 resulted in activation of ERK1/2 and JNK1 and up-regulation of collagenase-1 (MMP-1) and stromelysin-1 (MMP-3) production but did not induce MMP-13 expression. In addition, activation of p38 MAPK by constitutively active MKK6b or MKK3b was not sufficient to induce MMP-13 expression. These results show that TGF-beta-elicited induction of MMP-13 expression by gingival fibroblasts is dependent on the activity of p38 MAPK and the presence of functional AP-1 dimers. These observations demonstrate a fundamental difference in the regulation of collagenolytic capacity between gingival and dermal fibroblasts and suggest a role for MMP-13 in rapid turnover of collagenous matrix during repair of gingival wounds, which heal with minimal scarring.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65809]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Ravanti, L.,Hakkinen, L.,Larjava, H.,et al. Transforming growth factor-beta induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase[J],1999.
APA	Ravanti, L..,Hakkinen, L..,Larjava, H..,Saarialho-Kere, U..,Foschi, M..,...&韩家淮.(1999).Transforming growth factor-beta induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase..
MLA	Ravanti, L.,et al."Transforming growth factor-beta induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase".(1999).

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