title: Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug-Activated Gene 1 Counteracts Intestinal Ulcerative Injuries.
abstract: In response to ulcerative mucosal injuries, intestinal epithelial restitution is a critical event in the early defense against harmful attacks by luminal Ags. Based on the assumption that epithelial NAG-1 is an endogenous regulator of ulcerative stress-induced injuries, the expression and functions of NAG-1 were investigated. Genetic ablation of NAG-1 decreased survival of mice with dextran sodium sulfate-induced intestinal ulcer and histologically delayed the epithelial restitution, confirming early protective roles of NAG-1 in ulcerative insults. Moreover, enhanced expression of NAG-1 during the wound-healing process was associated with epithelial cell migration and spreading. In response to ulcerative injury, RhoA GTPase, a cytoskeleton modulator, mediated epithelial restitution via enhanced motility. RhoA expression was prominently elevated in the restituting epithelia cells around the insulted wound bed and was attenuated by NAG-1 deficiency. Pharmacological intervention with RhoA thus attenuated NAG-1-mediated epithelial cell migration during epithelial restitution. Taken together, epithelial restitution was promoted by enhanced NAG-1 expression and subsequent enterocyte locomotion during the early wound-healing process, suggesting clinical usefulness of NAG-1 as a novel endogenous muco-protective factor or an indicator of therapeutic efficacy against the ulcerative gastrointestinal diseases, including inflammatory bowel disease.
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea;
authors.forename: Hye Jin
authors.identifier: 0000-0001-6434-2526
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea;
authors.forename: Kee Hun
authors.initials: KH
authors.lastname: Do
authors.affiliation: Department of Pediatrics, Pusan National University, Yangsan 50612, Korea; and.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea;
authors.forename: Juil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea;
authors.forename: Mira
authors.initials: M
authors.lastname: Yu
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea;
authors.forename: Seong-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Korea; Research Institute for Basic Sciences, Immunoregulatory Therapeutics Group in Brain, Busan 21 Project, Yangsan 50612, South Korea moon@pnu.edu.
authors.forename: Yuseok
authors.initials: Y
authors.lastname: Moon
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002648:Child; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D020895:Enterocytes / Q000276:immunology*; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014456:Ulcer; D014945:Wound Healing / Q000502:physiology*; D055815:Young Adult
chemical_list: C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15