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http://purl.uniprot.org/citations/21683675 | http://www.w3.org/2000/01/rdf-schema#comment | "Entamoeba histolytica is a protozoan parasite that causes amebic dysentery characterized by severe watery diarrhea. Unfortunately, the parasitic factors involved in the pathogenesis of diarrhea are poorly defined. Prostaglandin E(2) (PGE(2)) is a host lipid mediator associated with diarrheal diseases. Intriguingly, E. histolytica produces and secretes this inflammatory molecule. We investigated the mechanism whereby ameba-derived PGE(2) induces the onset of diarrhea by altering ion permeability of paracellular tight junctions (TJs) in colonic epithelia. PGE(2) decreased barrier integrity of TJs in a dose- and time-dependent manner, as measured by transepithelial resistance. PGE(2) signals were selectively transduced via the EP4 receptor. Furthermore, PGE(2) signaling decreased TJ integrity, as revealed by EP receptor-specific agonist and antagonist studies. Loss of mucosal barrier integrity corresponded with increased ion permeability across TJs. Subcellular fractionation and confocal microscopy studies highlighted a significant spatial alteration of an important TJ protein, claudin-4, that corresponded with increased sodium ion permeability through TJs toward the lumen. Moreover, PGE(2)-induced luminal chloride secretion was a prerequisite for alterations at TJs. Thus, the gradient of NaCl created across epithelia could serve as a trigger for osmotic water flow that leads to diarrhea. Our results highlight a pathological role for E. histolytica-derived PGE(2) in the onset of diarrhea."xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajpath.2011.05.001"xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/author | "Moreau F."xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/author | "Lejeune M."xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/author | "Chadee K."xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/pages | "807-818"xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/title | "Prostaglandin E2 produced by Entamoeba histolytica signals via EP4 receptor and alters claudin-4 to increase ion permeability of tight junctions."xsd:string |
http://purl.uniprot.org/citations/21683675 | http://purl.uniprot.org/core/volume | "179"xsd:string |
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