Document Type

Article

Publication Date

5-1-2015

Comments

This is the peer reviewed version of the following article: de Miranda de Araujo, L. B., Horgan, C. E., Aron, A., Iozzo, R. V., & Lechner, B. E. (2015). Compensatory fetal membrane mechanisms between biglycan and decorin in inflammation. Molecular Reproduction and Development, 82(5), 387-396, which has been published in final form at DOI: 10.1002/mrd.22488. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

The published version is available at . Copyright ©

Abstract

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, Western blotting, and enzyme-linked immunosorbent assays. Our results suggest that biglycan and decorin compensate for each other in the fetal membranes, but lose the ability to do so under inflammation, leading to decreased latency to preterm birth. Furthermore, our findings suggest that biglycan and decorin play discrete roles in fetal membrane signaling pathways during inflammation, leading to changes in the abundance of MMP8 and collagen α1VI, two components of the fetal membrane extracellular matrix that influence the pathophysiology of PPROM. In summary, these findings underline the importance of biglycan and decorin as targets for the manipulation of fetal membrane extracellular matrix stability in the context of inflammation.

PubMed ID

25914258

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