Identification of a novel interaction between corticotropin releasing hormone (Crh) and macroautophagy.
Sci Rep
; 6: 23342, 2016 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-26987580
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Hormona Liberadora de Corticotropina
/
Sulfato de Dextran
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Colitis
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Grecia