Prevention of Inflammation-Associated Preterm Birth by Knockdown of the Endothelin-1–Matrix Metalloproteinase-1 Pathway

Wei Wang, Haoting Yen, Chih-Hung Chen, Nitesh Jasani, Rimabahen Soni, Karen Koscica, and Sandra E Reznik

Premature birth is an increasing health problem and is the major cause of neonatal mortality in developed countries. Intrauterine infection is often associated with preterm labor. The matrix metalloproteinases (MMPs) are a family of zinc-dependant endopeptidases that aid in the degradation of the extracellular matrix, allowing for cell movement and tissue reorganization thereby supporting the growing fetus. Endothelin-1 (ET-1), an extremely potent vasoconstrictor peptide, has been shown to increase myometrial smooth muscle tone. Blockade of ET-1 through endothelin-converting enzyme 1 (ECE-1) inhibitor or endothelin receptor antagonists prevents preterm labor and delivery in mice. Wang et al. demonstrate that LPS-induced preterm labor is associated with increased levels of MMP-1. Using ECE-1 RNAi, they show that silencing the ECE-1/ET-1 pathway prevents both the onset of preterm labor and MMP-1 upregulation. Their data indicate that ET-1 and MMP-1 act in the same molecular pathway in preterm labor.

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Posted by MolMed Admin on Nov 7, 2010 12:00 AM CDT