MT1-MMP-dependent and -independent regulation of gelatinase A activation in long-term, ascorbate-treated fibroblast cultures: Regulation by fibrillar collagen

Ruangpanit, Neeracha, Price, John T., Holmbeck, Kenn, Birkedal-Hansen, Henning, Guenzler, Volkmar, Huang, Xinfan, Chan, Danny, Bateman, John F., & Thompson, Erik W. (2002) MT1-MMP-dependent and -independent regulation of gelatinase A activation in long-term, ascorbate-treated fibroblast cultures: Regulation by fibrillar collagen. Experimental Cell Research, 272(2), pp. 109-118.

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Human skin fibroblasts were cultured long-term in the presence of ascorbic acid to allow formation of a three-dimensional collagen matrix, and the effects of this on activation of secreted matrix metalloproteinase-2 (MMP-2) were examined. Accumulation of collagen over time correlated with increased levels of both mature MMP-2 and cell-associated membrane type 1-MMP (MT1-MMP), and subsequently increased mRNA levels for MT1-MMP, providing temporal resolution of the "nontranscriptional" and "transcriptional" effects of collagen on MT-1MMP functionality. MMP-2 activation by these cultures was blocked by inhibitors of prolyl-4-hydroxylase, or when fibroblasts derived from the collagen α1(I) gene-deficient Mov-13 mouse were used. MMP-2 activation by the Mov-13 fibroblasts was rescued by transfection of a full-length α1(I) collagen cDNA, and to our surprise, also by transfection with an α1(I) collagen cDNA carrying a mutation at the C-proteinase cleavage, which almost abrogated fibrillogenesis. Although studies with ascorbate-cultured MT1-MMP-/- fibroblasts showed that MT1-MMP played a significant role in the collagen-induced MMP-2 activation, a residual MT1-MMP-independent activation of MMP-2 was seen which resembled the level of MMP-2 activation persisting when wild-type fibroblasts were cultured in the presence of both ascorbic acid and MMP inhibitors. We were also unable to block this residual activation with inhibitors specific for serinyl, aspartyl, or cysteinyl enzymes.

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ID Code: 72175
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):19
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 11777335
Additional URLs:
Keywords: Ascorbic acid, Collagen, Fibril, MMP-2 activation, MT1-MMP, pC-procollagen
DOI: 10.1006/excr.2001.5403
ISSN: 0014-4827
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 28 May 2014 02:05
Last Modified: 28 May 2014 02:05

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