Methotrexate mediates the integrity of intestinal stem cells partly through nitric oxide-dependent Wnt/β-catenin signaling in methotrexate-induced rat ileal mucositis

Maiko Machida; Takuji Machida; Masaki Kikuchi; Ayaka Shimizu; Syunsuke Ida; Yoshiki Tawaraya; Risa Kato; Keisuke Haramaki; Kaori Yama; Saki Shiga; Masahiko Hirafuji; Kenji Iizuka

Journal of Pharmacological Sciences (Mar 2022)

Methotrexate mediates the integrity of intestinal stem cells partly through nitric oxide-dependent Wnt/β-catenin signaling in methotrexate-induced rat ileal mucositis

Maiko Machida,
Takuji Machida,
Masaki Kikuchi,
Ayaka Shimizu,
Syunsuke Ida,
Yoshiki Tawaraya,
Risa Kato,
Keisuke Haramaki,
Kaori Yama,
Saki Shiga,
Masahiko Hirafuji,
Kenji Iizuka

Affiliations

Maiko Machida: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Takuji Machida: Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan; Corresponding author. Fax: +81 133 23 1379
Masaki Kikuchi: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Ayaka Shimizu: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Syunsuke Ida: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Yoshiki Tawaraya: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Risa Kato: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Keisuke Haramaki: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Kaori Yama: Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan
Saki Shiga: Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan
Masahiko Hirafuji: Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan
Kenji Iizuka: Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido, 061-0293, Japan

Journal volume & issue: Vol. 148, no. 3
pp. 281 – 285

Abstract

Read online

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/β-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/β-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/β-catenin signaling and may enhance tolerability to methotrexate-induced injury.

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

About the journal

Abstract

Keywords