5-Aza-2'-deoxycytidine and interleukin-1 cooperate to regulate matrix metalloproteinase-3 gene expression

Couillard, Julie; Esteve, Pierre-Olivier; Pradhan, Sriharsa et St-Pierre, Yves ORCID: https://orcid.org/0000-0002-1948-2041 (2011). 5-Aza-2'-deoxycytidine and interleukin-1 cooperate to regulate matrix metalloproteinase-3 gene expression International Journal of Cancer , vol. 129 , nº 9. pp. 2083-2092. DOI: 10.1002/ijc.25865.

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Résumé

Members of the matrix metalloproteinase (MMP) family of enzymes play a crit. role in extracellular matrix remodeling in a no. of normal and pathol. processes. Accordingly, activation of MMP gene expression is tightly regulated at the level of transcription by specific transcription factors, most notably following exposure to inflammatory cytokines. Recent studies with 5-aza-2'-deoxycytidine (5-aza-dC), a specific DNA methylase inhibitor, also suggest that epigenetic processes contribute to the regulation of MMP expression. Although inflammation-related aberrant patterns of DNA methylation have been described, a mechanistic link between inflammation and epigenetic alterations in the control of MMP expression remains unclear. Here, we provide evidence that increased MMP-3 expression by 5-aza-dC is modulated by interleukin-1 (IL-1). More specifically, we found that stimulation with IL-1, but not with IL-6 or TNFα, significantly increased the hypomethylation status of the MMP-3 promoter to a level similar to that found in dnmt1/dnmt3b-deficient HCT116 (DKO) cells. Furthermore, we showed that increased MMP-3 expression by 5-aza-dC was assocd. with increased expression and activity of specific transcription factors known to regulate MMP-3 expression. In fact, treatment with 5-aza-dC was obligatory for some transcription factors to trigger an increase in MMP-3 expression, such as Ap-1. In contrast, CCAAT enhancer-binding proteins and E-twenty six were capable of inducing MMP-3 alone. Overall, these findings provide a novel perspective of the collaborative role of 5-aza-dC and inflammatory cytokines with specific transcription factors that are normally involved in MMP-3 expression.

Type de document:	Article
Mots-clés libres:	matrix metalloproteinase; MMP-3; IL-1; DNA methylation; gene expression
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	09 mars 2024 22:21
Dernière modification:	09 mars 2024 22:21
URI:	https://espace.inrs.ca/id/eprint/14519

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