| Prevention of inflammation-associated preterm birth by knockdown of the endothelin-1-matrix metalloproteinase-1 pathway. | |
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MedLine Citation:
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PMID: 20809048 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Premature delivery occurs in 12% of all births, accounts for nearly half of neonatal morbidity and is increasing in frequency. Current therapeutic approaches to preterm delivery are ineffective and present serious risks to both the mother and fetus. Although there are multiple factors that contribute to the etiology of preterm birth, the single most common cause is infection. Recently, using cDNA microarray analysis of human placental tissue, we demonstrated that human placental matrix metalloproteinase-1 (MMP-1) is upregulated during labor. In a separate line of investigation, we have shown that blockade of endothelin-1 (ET-1) action through the use of an endothelin-converting enzyme-1 (ECE-1) inhibitor, an established commercially available endothelin receptor antagonist or a novel quinolone-derived endothelin receptor antagonist synthesized by our group also prevents preterm labor and delivery in a mouse model. We have now shown that induction of preterm labor with lipopolysaccharide in our mouse model is associated with increased levels of MMP-1. Furthermore, we showed that silencing the ECE-1/ET-1 pathway by using ECE-1 RNA interference prevents both the onset of preterm labor and upregulation of MMP-1. The data indicate that ET-1 and MMP-1 act in the same molecular pathway in preterm labor. |
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Authors:
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Wei Wang; Haoting Yen; Chih-Hung Chen; Nitesh Jasani; Rimabahen Soni; Karen Koscica; Sandra E Reznik |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-18 |
Journal Detail:
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Title: Molecular medicine (Cambridge, Mass.) Volume: 16 ISSN: 1528-3658 ISO Abbreviation: Mol. Med. Publication Date: 2010 Nov-Dec |
Date Detail:
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Created Date: 2010-11-05 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9501023 Medline TA: Mol Med Country: United States |
Other Details:
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Languages: eng Pagination: 505-12 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York, United States of America. |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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1K08HD1209/HD/NICHD NIH HHS |
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