Identification of a novel interaction between corticotropin releasing hormone (Crh) and macroautophagy

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 macroautoph...

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Bibliographic Details
Published in:Scientific reports 2016-03, Vol.6 (1), p.23342-23342, Article 23342
Main Authors: Giannogonas, Panagiotis, Apostolou, Athanasia, Manousopoulou, Antigoni, Theocharis, Stamatis, Macari, Sofia A., Psarras, Stelios, Garbis, Spiros D., Pothoulakis, Charalabos, Karalis, Katia P.
Format: Article
Language:English
Subjects:
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Adenine - analogs & derivatives
Adenine - pharmacology
Amino acids
Animal models
Animals
Autophagy
Autophagy - drug effects
Cells, Cultured
Colitis
Colitis - chemically induced
Colitis - genetics
Colitis - metabolism
Corticotropin-releasing hormone
Corticotropin-Releasing Hormone - genetics
Corticotropin-Releasing Hormone - metabolism
Dextran Sulfate - toxicity
Digestive system
Disease Models, Animal
Epithelium
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - metabolism
Gastrointestinal tract
Gastrointestinal Tract - metabolism
Gene Knockout Techniques
Humanities and Social Sciences
Inflammatory bowel disease
Inflammatory bowel diseases
Intestine
Lipopolysaccharides
Male
Mice
multidisciplinary
Phagocytosis
Proteomics - methods
RAW 264.7 Cells
Rodents
Science
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep23342