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Regulation of MT1-MMP/MMP-2/TIMP-2 axis in human placenta

Authors Vincent Z, Mitchell M, Ponnampalam A

Received 6 May 2015

Accepted for publication 8 July 2015

Published 3 October 2015 Volume 2015:8 Pages 193—200

DOI https://doi.org/10.2147/JIR.S88039

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Ning Quan


Zoë L Vincent,1,2 Murray D Mitchell,l,3 Anna P Ponnampalam1,2

1Liggins Institute, 2Gravida: National Centre for Growth and Development, University of Auckland, Auckland, New Zealand; 3University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia

Abstract: Matrix metalloproteinases (MMPs) and specific endogenous tissue inhibitors of metalloproteinases (TIMPs) mediate rupture of the fetal membranes in both physiological and pathological conditions. MMPs and TIMPs are subject to regulation by DNA methylation in human malignancies and pre-eclampsia. To determine if membrane type 1 MMP (MT1-MMP), MMP2, and TIMP2 are regulated by DNA methylation in human placentas, we employed an in vitro model where human placental tissues were collected at term gestation and cultured with methylation inhibiting agent 5-aza-2′deoxycytidine (AZA) and lipopolysaccharide. The results suggest that DNA methylation is not directly involved in the regulation of MT1-MMP in placental tissue; however, remodeling of chromatin by a pharmacologic agent such as AZA potentiates an infection-related increase in MT1-MMP. MT1-MMP is a powerful activator of MMP2 and this action, coupled with either no change or a decrease in TIMP2 concentrations, favors a gelatinolytic state leading to extracellular matrix degradation, which could predispose fetal membranes to rupture prematurely during inflammation.

Keywords: placenta, epigenetic regulation, DNA methylation, MMPs, labor

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