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Methotrexate mediates the integrity of intestinal stem cells partly through nitric oxide-dependent Wnt/ß-catenin signaling in methotrexate-induced rat ileal mucositis.
Machida, Maiko; Machida, Takuji; Kikuchi, Masaki; Shimizu, Ayaka; Ida, Syunsuke; Tawaraya, Yoshiki; Kato, Risa; Haramaki, Keisuke; Yama, Kaori; Shiga, Saki; Hirafuji, Masahiko; Iizuka, Kenji.
Afiliación
  • Machida M; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Machida T; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan. Electronic address: tmachida@hoku-iryo-u.ac.jp.
  • Kikuchi M; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Shimizu A; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Ida S; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Tawaraya Y; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Kato R; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Haramaki K; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Yama K; Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  • Shiga S; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan.
  • Hirafuji M; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan.
  • Iizuka K; Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan.
J Pharmacol Sci ; 148(3): 281-285, 2022 Mar.
Article en En | MEDLINE | ID: mdl-35177206
This study aimed to elucidate the role of nitric oxide (NO) in intestinal stem cells in methotrexate-induced ileal mucositis in rats. Methotrexate induced the mRNA expressions of the Wnt/ß-catenin target genes Wnt3a, Sox9, and Lgr5 and the Wnt-antagonist gene sFRP-1 and the protein expressions of Lgr5 and sFRP-1. Methotrexate also induced Lgr5+ cells and lysozyme+ cells. A non-selective NO inhibitor inhibited the methotrexate induction of Wnt/ß-catenin target genes and Lgr5+ cells but enhanced that of sFRP-1 expression. Thus, methotrexate mediates the integrity of intestinal stem cells partly through NO-dependent Wnt/ß-catenin signaling and may enhance tolerability to methotrexate-induced injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Transducción de Señal / Metotrexato / Mucositis / Proteínas Wnt / Beta Catenina / Íleon / Intestinos / Óxido Nítrico Límite: Animals Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Transducción de Señal / Metotrexato / Mucositis / Proteínas Wnt / Beta Catenina / Íleon / Intestinos / Óxido Nítrico Límite: Animals Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón