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J Pharmacol Sci
; 148(3): 281-285, 2022 Mar.
Article
in English
| MEDLINE
| ID: mdl-35177206
ABSTRACT
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.
Subject(s)
Ileum , Intestines/cytology , Intestines/drug effects , Methotrexate/adverse effects , Mucositis/genetics , Mucositis/pathology , Nitric Oxide/physiology , Signal Transduction/drug effects , Signal Transduction/genetics , Stem Cells/drug effects , Stem Cells/pathology , Wnt Proteins/metabolism , beta Catenin/metabolism , Animals , Gene Expression/drug effects , Male , Mucositis/chemically induced , Nitric Oxide/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Wistar
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