title: 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, 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.
authors.affiliation: From the Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and.
authors.forename: Mayo
authors.initials: M
authors.lastname: Nishitani
authors.affiliation: the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takakura
authors.affiliation: the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Imai
authors.affiliation: the Department of Biochemistry, School of Medicine, Niigata University, Niigata 951-8510, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: From the Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and h-kawashima@hoshi.ac.jp.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D003093:Colitis, Ulcerative / Q000517:prevention & control*; D003106:Colon / Q000276:immunology / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology; D009093:Mucus / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; D016207:Cytokines; D008869:Microtubule-Associated Proteins; D000071193:Autophagy-Related Protein 7
keywords: antimicrobial peptide (AMP); autophagy; bacteria; colitis; intestinal epithelium; mucin