title: Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway.
abstract: Previous studies have shown that carbon monoxide (CO) is involved in a variety of physiological and pathophysiological processes including anti-inflammatory, anti-apoptotic and anti-oxidant responses. However, it remains unclear whether CO promotes gastric ulcer healing. In the present study, we evaluated the efficacy of CO-saturated saline in the treatment of gastric ulcers and its underlying mechanism. Acute gastric ulcers were induced in C57BL/6 male mice using acetic acid. A CO-saturated solution was prepared by bubbling 50% CO gas into saline. To investigate the effect of CO on gastric mucosal healing, CO solution was orally administrated twice a day beginning on day 3 after the induction of gastric ulcer. Mice were sacrificed on day 7 after ulcer induction. The stomach was removed, and the ulcerated lesions were measured. In vitro wound healing assays were used to determine the mechanism of action of CO in the restoration of murine gastric epithelial cells. The oral administration of CO solution accelerated the gastric ulcer healing by promoting re-epithelialization. Furthermore, the wound healing assay performed using the murine gastric epithelial cells revealed that the CO-saturated medium enhanced cell migration through the activation of protein kinase C (PKC). Based on these data, CO may represent a novel therapeutic approach for the treatment of gastric mucosal injuries.
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizuhima
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Horie
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Hirata
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Tsuboi
authors.affiliation: a Department of Molecular Gastroenterology and Hepatology , Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto , Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism; D013276:Stomach Ulcer / Q000628:therapy*; D014945:Wound Healing
chemical_list: D002248:Carbon Monoxide; D011493:Protein Kinase C
keywords: Carbon monoxide; gastric ulcer; protein kinase C; re-epithelialization; wound healing