title: The arachidonic acid metabolite 11β-ProstaglandinF2α controls intestinal epithelial healing: deficiency in patients with Crohn's disease.
abstract: In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. In Crohn's Disease (CD), both EGC phenotype and IEB functions are altered, but putative involvement of EGC in CD pathogenesis remains unknown and study of human EGC are lacking. EGC isolated from CD and control patients showed similar expression of glial markers and EGC-derived soluble factors (IL6, TGF-β, proEGF, GSH) but CD EGC failed to increase IEB resistance and healing. Lipid profiling showed that CD EGC produced decreased amounts of 15-HETE, 18-HEPE, 15dPGJ2 and 11βPGF2α as compared to healthy EGC. They also had reduced expression of the L-PGDS and AKR1C3 enzymes. Produced by healthy EGC, the 11βPGF2 activated PPARγ receptor of intestinal epithelial cells to induce cell spreading and IEB wound repair. In addition to this novel healing mechanism our data show that CD EGC presented impaired ability to promote IEB functions through defect in L-PGDS-AKR1C3-11βPGF2α dependent pathway.
authors.affiliation: INSERM, UMR913, Nantes, F-44093, France.|Université Nantes, Nantes, F-44093, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, F-44093, France.|Centre de Recherche en Nutrition Humaine, Nantes, F-44093, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Coquenlorge
authors.affiliation: INSERM, UMR913, Nantes, F-44093, France.|Université Nantes, Nantes, F-44093, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, F-44093, France.|Centre de Recherche en Nutrition Humaine, Nantes, F-44093, France.
authors.forename: Laurianne
authors.initials: L
authors.lastname: Van Landeghem
authors.affiliation: INSERM, UMR913, Nantes, F-44093, France.|Université Nantes, Nantes, F-44093, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, F-44093, France.|Centre de Recherche en Nutrition Humaine, Nantes, F-44093, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Jaulin
authors.affiliation: Centre de Pathophysiologie, CHU Purpan, Toulouse, France.|INSERM UMR-1043 CNRS UMR-5282, Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cenac
authors.affiliation: Centre de Pathophysiologie, CHU Purpan, Toulouse, France.|INSERM UMR-1043 CNRS UMR-5282, Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.affiliation: INSERM, UMR913, Nantes, F-44093, France.|Université Nantes, Nantes, F-44093, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, F-44093, France.|Centre de Recherche en Nutrition Humaine, Nantes, F-44093, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Duchalais
authors.affiliation: INSERM, UMR913, Nantes, F-44093, France.|Université Nantes, Nantes, F-44093, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, F-44093, France.|Centre de Recherche en Nutrition Humaine, Nantes, F-44093, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
authors.affiliation: INSERM, UMR913, Nantes, F-44093, France.|Université Nantes, Nantes, F-44093, France.|Institut des Maladies de l'Appareil Digestif, CHU Nantes, Hôpital Hôtel-Dieu, Nantes, F-44093, France.|Centre de Recherche en Nutrition Humaine, Nantes, F-44093, France.
authors.forename: Malvyne
authors.initials: M
authors.lastname: Rolli-Derkinderen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074425:Aldo-Keto Reductase Family 1 Member C3 / Q000378:metabolism; D018938:Caco-2 Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D003424:Crohn Disease / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D014945:Wound Healing; D055815:Young Adult
chemical_list: C477819:15-deoxyprostaglandin J2; C561691:18(R)-hydroxyeicosapentaenoic acid; D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D015118:Eicosapentaenoic Acid; D015237:Dinoprost; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D015230:Prostaglandin D2