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


ABSTRACT: 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, Relm?, 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.

SUBMITTER: Tsuboi K 

PROVIDER: S-EPMC4536456 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Tsuboi Koichiro K   Nishitani Mayo M   Takakura Atsushi A   Imai Yasuyuki Y   Komatsu Masaaki M   Kawashima Hiroto H  

The Journal of biological chemistry 20150706 33


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 reve  ...[more]

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