期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 19, 页码 13295-13307出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.550541
关键词
Cyclooxygenase (COX) Pathway; Fibronectin; Matrix Metalloproteinase (MMP); Prostaglandins; Thrombin; Amnion; Decidua; Fetal Membrane; Protease-activated Receptor-1
资金
- National Institutes of Health [HD11149]
- SUMITOMO Life Social Welfare Service Foundation
- Human Tissue and Biologic Fluid Core Laboratory
- Grants-in-Aid for Scientific Research [24119004, 25861488] Funding Source: KAKEN
Background: Bleeding during pregnancy is a risk factor for premature rupture of the fetal membranes. Results: Thrombin causes preterm birth in mice and activates PAR-1 and TLR4 to increase MMPs and COX-2. Conclusion: Thrombin acts through multiple mechanisms to increase MMPs and PGE(2) in amnion. Significance: Thrombin plays a pivotal role in the pathogenesis of preterm labor and rupture of the membranes. Here, we investigated the effects of thrombin on matrix metalloproteinases (MMPs) and prostaglandin (PG) synthesis in fetal membranes. Thrombin activity was increased in human amnion from preterm deliveries. Treatment of mesenchymal, but not epithelial, cells with thrombin resulted in increased MMP-1 and MMP-9 mRNA and enzymatic activity. Thrombin also increased COX2 mRNA and PGE(2) in these cells. Protease-activated receptor-1 (PAR-1) was localized to amnion mesenchymal and decidual cells. PAR-1-specific inhibitors and activating peptides indicated that thrombin-induced up-regulation of MMP-9 was mediated via PAR-1. In contrast, thrombin-induced up-regulation of MMP-1 and COX-2 was mediated through Toll-like receptor-4, possibly through thrombin-induced release of soluble fetal fibronectin. In vivo, thrombin-injected pregnant mice delivered preterm. Mmp8, Mmp9, and Mmp13, and PGE(2) content was increased significantly in fetal membranes from thrombin-injected animals. These results indicate that thrombin acts through multiple mechanisms to activate MMPs and PGE2 synthesis in amnion.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据