title: Fetal fibronectin signaling induces matrix metalloproteases and cyclooxygenase-2 (COX-2) in amnion cells and preterm birth in mice.
abstract: 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 E(2) synthesis, activating both NFκB and ERK1/2 signaling. Fetal FN-induced increases in MMPs and COX-2 were mediated through its extra domain A and Toll-like receptor 4 expressed in mesenchymal cells. Lipopolysaccharide and TNF-α 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Haruta
authors.initials: H
authors.lastname: Mogami
authors.forename: Annavarapu Hari
authors.initials: AH
authors.lastname: Kishore
authors.forename: Haolin
authors.initials: H
authors.lastname: Shi
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Keller
authors.forename: Yucel
authors.initials: Y
authors.lastname: Akgul
authors.forename: R Ann
authors.initials: RA
authors.lastname: Word
mesh_terms: D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000819:agonists / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005333:Fetus; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000201:enzymology*; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005326:Fetal Proteins; D005353:Fibronectins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone