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Publication : Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus.

First Author  Tsuboi K Year  2015
Journal  J Biol Chem Volume  290
Issue  33 Pages  20511-26
PubMed ID  26149685 Mgi Jnum  J:251756
Mgi Id  MGI:6102047 Doi  10.1074/jbc.M114.632257
Citation  Tsuboi K, et al. (2015) Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus. J Biol Chem 290(33):20511-26
abstractText  Genome-wide association studies of inflammatory bowel diseases identified susceptible loci containing an autophagy-related gene. However, the role of autophagy in the colon, a major affected area in inflammatory bowel diseases, is not clear. Here, we show that colonic epithelial cell-specific autophagy-related gene 7 (Atg7) conditional knock-out (cKO) mice showed exacerbation of experimental colitis with more abundant bacterial invasion into the colonic epithelium. Quantitative PCR analysis revealed that cKO mice had abnormal microflora with an increase of some genera. Consistently, expression of antimicrobial or antiparasitic peptides such as angiogenin-4, Relmbeta, intelectin-1, and intelectin-2 as well as that of their inducer cytokines was significantly reduced in the cKO mice. Furthermore, secretion of colonic mucins that function as a mucosal barrier against bacterial invasion was also significantly diminished in cKO mice. Taken together, our results indicate that autophagy in colonic epithelial cells protects against colitis by the maintenance of normal gut microflora and secretion of mucus.
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