Fetal Fibronectin Signaling Induces Matrix Metalloproteases and Cyclooxygenase-2 (COX-2) in Amnion Cells and Preterm Birth in Mice
Fetal Fibronectin Signaling Induces Matrix Metalloproteases and Cyclooxygenase-2 (COX-2) in Amnion Cells and Preterm Birth in Mice
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DOI：
10.1074/jbc.m112.424366
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发表时间：
2013-01-18
影响因子：
4.8
通讯作者：
Word, R. Ann
中科院分区：
文献类型：
--
作者：
Mogami, Haruta;Kishore, Annavarapu Hari;Word, R. Ann
子宫颈和阴道分泌物中的胎儿纤连蛋白（fFN）已被用作早产的预测因子。在这里，我们阐明了fFN对细胞类型特异性基质金属蛋白酶（MMPs）和前列腺素合成在胎膜中的病理功能。用fFN处理羊膜间充质细胞导致MMP-1和MMP-9 mRNA和酶活性以及考克斯-2 mRNA和前列腺素E-2合成显著增加，激活NF κ B B和ERK 1/2信号传导。胎儿FN诱导的MMPs和考克斯-2的增加是通过间充质细胞中表达的其额外结构域A和Toll样受体4介导的。脂多糖和TNF-α增加培养的羊膜上皮细胞培养液中游离FN的释放。最后，在妊娠小鼠中注射fFN导致早产。总的来说，这些结果表明，fFN不仅是早产的标志物，而且在早产和胎膜早破的发病机制中起着重要作用。
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 NF kappa B 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-alpha 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.