title: Identification of a novel interaction between corticotropin releasing hormone (Crh) and macroautophagy.
abstract: In inflammatory bowel disease (IBD), compromised restitution of the epithelial barrier contributes to disease severity. Owing to the complexity in the pathogenesis of IBD, a variety of factors have been implicated in its progress. In this study, we report a functional interaction between macroautophagy and Corticotropin Releasing Hormone (Crh) in the gut. For this purpose we used DSS colitis model on Crh -/- or wild-type (wt) with pharmacological inhibition of autophagy. We uncovered sustained basal autophagy in the gut of Crh -/- mice, which persisted over the course of DSS administration. Autophagy inhibition resulted in partial rescue of Crh -/- mice, while it increased the expression of Crh in the wt gut. Similarly, Crh deficiency was associated with sustained activation of base line autophagy. In vitro models of amino acid deprivation- and LPS-induced autophagy confirmed the in vivo findings. Our results indicate a novel role for Crh in the intestinal epithelium that involves regulation of autophagy, while suggesting the complementary action of the two pathways. These data suggest the intriguing possibility that targeting Crh stimulation in the intestine may provide a novel therapeutic approach to support the integrity of the epithelial barrier and to protect from chronic colitis.
authors.affiliation: Clinical, Experimental Surgery, &Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.|Faculty of Medicine, University of Crete, 71003, Iraklion, Crete, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Giannogonas
authors.affiliation: Clinical, Experimental Surgery, &Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.|Faculty of Medicine, School of Health Sciences, University of Athens, 11527, Athens, Greece.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Apostolou
authors.affiliation: Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.|Clinical and Experimental Sciences Unit, University of Southampton, Faculty of Medicine, SO16 6YD, Southampton, UK.
authors.forename: Antigoni
authors.initials: A
authors.lastname: Manousopoulou
authors.affiliation: Faculty of Medicine, School of Health Sciences, University of Athens, 11527, Athens, Greece.
authors.forename: Stamatis
authors.initials: S
authors.lastname: Theocharis
authors.affiliation: Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.|Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton SO16 6YD, United Kingdom.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Macari
authors.affiliation: Cell Biology Division, Center of Basic Research I, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.
authors.forename: Stelios
authors.initials: S
authors.lastname: Psarras
authors.affiliation: Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.|Clinical and Experimental Sciences Unit, University of Southampton, Faculty of Medicine, SO16 6YD, Southampton, UK.|Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton SO16 6YD, United Kingdom.
authors.forename: Spiros D
authors.initials: SD
authors.lastname: Garbis
authors.affiliation: Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, 90095, Los Angeles, CA, USA.
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
authors.affiliation: Clinical, Experimental Surgery, &Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.|Division of Endocrinology, Children's Hospital, 02115, Boston, MA, USA.
authors.forename: Katia P
authors.initials: KP
authors.lastname: Karalis
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D040901:Proteomics / Q000379:methods; D000067996:RAW 264.7 Cells
chemical_list: C025946:3-methyladenine; D003346:Corticotropin-Releasing Hormone; D016264:Dextran Sulfate; D000225:Adenine