title: Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach.
abstract: Chronic inflammation contributes to a wide variety of human disorders. In the stomach, longstanding gastritis often results in structural alterations in the gastric mucosa, including metaplastic changes and gastric cancers. Therefore, it is important to elucidate factors that are involved in gastric inflammation. Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins. Here, we have demonstrated that Nrdc crucially regulates gastric inflammation caused by Helicobacter felis infection or forced expression of prostaglandin E2in K19-C2mE mice. Metaplastic changes following gastric inflammation were suppressed by the deletion of Nrdc. Furthremore, the deletion of Nrdc significantly suppressed N-methyl-N-nitrosourea (MNU)-induced gastric tumorigenesis in the murine stomach. These data may lead to a global therapeutic approach against various gastric disorders by targeting Nrdc.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192 Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Oshima
authors.affiliation: Division of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192 Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nishi
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seno
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005756:Gastritis / Q000473:pathology*; D016481:Helicobacter Infections / Q000473:pathology*; D044922:Helicobacter felis / Q000254:growth & development*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008679:Metaplasia / Q000473:pathology*; D051379:Mice; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology*
chemical_list: D008666:Metalloendopeptidases; C087976:nardilysin