期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/srep23342
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资金
- FT-MS instrumentation at the University of Southampton
- European Union (European Social Fund - ESF)
- Greek National Funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II
- European Social Fund, EU-FP7 TransMed [245928]
- NIH [P01-DK 33506]
- International Highly Cited Research Group of the Deanship of Scientific Research [IHCRG 14-203]
- Vice-Dean of Scientific Research Chairs
- Visiting Professor Program of King Saud University, Riyadh, Saudi Arabia
- Wessex Cancer Trust
- Wessex Medical Research Trust, U.K
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.
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