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Autophagy. 2013 Aug;9(8):1188-200. doi: 10.4161/auto.24797. Epub 2013 May 8.

ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.

Author information

1
Departamento de Bioquímica y Biología Molecular; Facultad de Medicina; Instituto Universitario de Oncología (IUOPA); Universidad de Oviedo; Oviedo, Spain.

Abstract

The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b (-/-) mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b (-/-) mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency.

KEYWORDS:

ATG4B; Paneth cell; autophagin-1; autophagy; colitis; cysteine peptidase; inflammation; intestinal homeostasis

PMID:
23782979
PMCID:
PMC3748191
DOI:
10.4161/auto.24797
[Indexed for MEDLINE]
Free PMC Article
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