Journal of Biological Chemistry 2015-08-14

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

Koichiro Tsuboi, Mayo Nishitani, Atsushi Takakura, Yasuyuki Imai, Masaaki Komatsu, Hiroto Kawashima

Index: J. Biol. Chem. 290 , 20511-26, (2015)

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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, Relmβ, 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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.