title: PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth.
abstract: The ductus arteriosus (DA) is a fetal shunt that directs right ventricular outflow away from pulmonary circulation and into the aorta. Critical roles for prostaglandin E(2) (PGE(2)) and the EP4 receptor (EP4) have been established in maintaining both the patency of the vessel in utero and in its closure at birth. Here we have generated mice in which loss of EP4 expression is limited to either the smooth muscle (SMC) or endothelial cells and demonstrated that SMC, but not endothelial cell expression of EP4 is required for DA closure. The genome wide expression analysis of full term wild type and EP4(-/-) DA indicates that PGE(2)/EP4 signaling modulates expression of a number of unique pathways, including those involved in SMC proliferation, cell migration, and vascular tone. Together this supports a mechanism by which maturation and increased contractility of the vessel is coupled to the potent smooth muscle dilatory actions of PGE(2).
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248, USA.
authors.forename: Artiom
authors.initials: A
authors.lastname: Gruzdev
authors.forename: MyTrang
authors.initials: M
authors.lastname: Nguyen
authors.forename: Martina
authors.initials: M
authors.lastname: Kovarova
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
mesh_terms: D000818:Animals; D002465:Cell Movement; D015232:Dinoprostone / Q000235:genetics* / Q000378:metabolism; D004373:Ductus Arteriosus / Q000378:metabolism*; D015870:Gene Expression; D016678:Genome; D051379:Mice; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics* / Q000378:metabolism
chemical_list: D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone