Fetal fibronectin signaling induces matrix metalloproteases and cyclooxygenase-2 (COX-2) in amnion cells and preterm birth in mice

Haruta Mogami, Annavarapu Hari Kishore, Haolin Shi, Patrick W. Keller, Yucel Akgul, R. Ann Word

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background: The function of fetal fibronectin (fFN) in the pathogenesis of preterm labor is not known. Results: fFN activates MMP-1, MMP-9, and COX-2 in mesenchymal cells and causes preterm labor in mice. Conclusion: fFN is biologically active and plays a significant role in the pathogenesis of preterm labor. Significance: Signaling of fFN in fetal membranes is important in the pathophysiology of premature preterm rupture of the membranes. Fetal fibronectin (fFN) in cervical and vaginal secretions has been used as a predictor of preterm delivery. Here, we clarified the pathological function of fFN on cell type-specific matrix metalloproteinases (MMPs) and prostaglandin synthesis in fetal membranes. Treatment of amnion mesenchymal cells with fFN resulted in dramatic increases in MMP-1 and MMP-9 mRNA and enzymatic activity as well as COX-2 mRNA and prostaglandin E2 synthesis, activating both NFB and ERK1/2 signaling. Fetal FN-induced increases inMMPsand COX-2 were mediated through its extra domainAand Toll-like receptor 4 expressed in mesenchymal cells. Lipopolysaccharide and TNF-increased the release of free FN in medium of amnion epithelial cells in culture. Finally, injection of fFN in pregnant mice resulted in preterm birth. Collectively, these results indicate that fFN is not only a marker of preterm delivery but also plays a significant role in the pathogenesis of preterm labor and premature rupture of fetal membranes.

Original languageEnglish (US)
Pages (from-to)1953-1966
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number3
DOIs
StatePublished - Jan 18 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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