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PGI 2 Inhibits Intestinal Epithelial Permeability and Apoptosis to Alleviate Colitis

Abstract : Background & Aims Inflammatory bowel diseases (IBDs) that encompass both ulcerative colitis and Crohn’s disease are a major public health problem with an etiology that has not been fully elucidated. There is a need to improve disease outcomes and preventive measures by developing new effective and lasting treatments. Although polyunsaturated fatty acid metabolites play an important role in the pathogenesis of several disorders, their contribution to IBD is yet to be understood. Methods Polyunsaturated fatty acids metabolite profiles were established from biopsy samples obtained from Crohn’s disease, ulcerative colitis, or control patients. The impact of a prostaglandin I2 (PGI2) analog on intestinal epithelial permeability was tested in vitro using Caco-2 cells and ex vivo using human or mouse explants. In addition, mice were treated with PGI2 to observe dextran sulfate sodium (DSS)-induced colitis. Tight junction protein expression, subcellular location, and apoptosis were measured in the different models by immunohistochemistry and Western blotting. Results A significant reduction of PGI2 in IBD patient biopsies was identified. PGI2 treatment reduced colonic inflammation, increased occludin expression, decreased caspase-3 cleavage and intestinal permeability, and prevented colitis development in DSS-induced mice. Using colonic explants from mouse and human control subjects, the staurosporine-induced increase in paracellular permeability was prevented by PGI2. PGI2 also induced the membrane location of occludin and reduced the permeability observed in colonic biopsies from IBD patients. Conclusions The present study identified a PGI2 defect in the intestinal mucosa of IBD patients and demonstrated its protective role during colitis.
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https://www.hal.inserm.fr/inserm-03287962
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Submitted on : Thursday, August 19, 2021 - 10:36:05 AM
Last modification on : Wednesday, October 20, 2021 - 3:19:34 AM

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Camille Pochard, Jacques Gonzales, Anne Bessard, Maxime Mahe, Arnaud Bourreille, et al.. PGI 2 Inhibits Intestinal Epithelial Permeability and Apoptosis to Alleviate Colitis. Cellular and Molecular Gastroenterology and Hepatology, Philadelphia, PA : American Gastroenterological Association, [2015]-, 2021, 12 (3), pp.1037-1060. ⟨10.1016/j.jcmgh.2021.05.001⟩. ⟨inserm-03287962v2⟩

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