title: The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis.
abstract: Accumulating evidence suggests that reactive oxygen species (ROS) generated by endogenous metabolic enzymes are involved in a variety of intracellular mechanisms. In particular, superoxide-generating NADPH oxidase (Nox) 1 is highly expressed in the colon and has been implicated in physiological and pathophysiological states of colon tissues. However, its role in tissue repair following colitis has not been fully elucidated. Our study using experimental colitis in mice showed that repair of the mucosal layer did not occur in Nox1-deficient mice following dextran sulfate sodium-induced colitis. This was accompanied by inhibition of proliferation, cell survival, migration, and terminal differentiation (generation of goblet cells) of crypt progenitor cells, as determined by histochemical analyses. Furthermore, Nox1 expression as well as ROS production in the colon crypt was increased during the repair process, and Nox1 deficiency suppressed these events. The results suggest that Nox1 promotes colon mucosal wound repair by sustaining the bioactivity of crypt progenitor cells and plays a crucial role in the epithelial restitution in the case of damage associated with colitis.
authors.affiliation: Department of Molecular Biology and Biochemistry, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kato
authors.forename: Masaya
authors.initials: M
authors.lastname: Marumo
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Misaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
authors.forename: Tohru
authors.initials: T
authors.lastname: Kamata
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D003106:Colon; D016264:Dextran Sulfate; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000074624:NADPH Oxidase 1; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012038:Regeneration
chemical_list: D017382:Reactive Oxygen Species; D016264:Dextran Sulfate; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse