Irsogladine maleate ameliorates infl ammation and fi brosis in mice with chronic colitis induced by dextran sulfate sodium

Hana Yamaguchi, Kenji Suzuki, Masaki Nagata, Tomoyuki Kawase, Vijayakumar Sukumaran, Rajarajan A. Thandavarayan, Yusuke Kawauchi, Junji Yokoyama, Masayuki Tomita, Hiroshi Kawachi, Kenichi Watanabe, Hiroyuki Yoneyama, Hitoshi Asakura, Ritsuo Takagi

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Intestinal fi brosis is a common and severe complication of infl ammatory bowel disease (IBD), especially Crohn's disease (CD). To investigate the therapeutic approach to intestinal fi brosis, we have developed a mouse model of intestinal fi brosis by administering dextran sulfate sodium (DSS) and examining the effects of irsogladine maleate (IM) [2,4-diamino-6-(2,5- dichlorophenyl)-s-triazine maleate], which has been widely used as an antiulcer drug for gastric mucosa in Japan, on DDS-induced chronic colitis. In this experimental colitis lesion, several pathognomonic changes were found: increased deposition of collagen, increased number of profi brogenic mesenchymal cells such as fi broblasts (vimentin+, 〈-SMA) and myofi broblasts (vimentin+, 〈-SMA+) in both mucosa and submucosa of the colon with infi ltrating infl ammatory cells, and increased mRNA expressions of collagen type I, transforming growth factor (TGF)-®, matrix metalloproteinase (MMP)-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. When IM was administered intrarectally to this colitis, all these pathological changes were signifi cantly decreased or suppressed, suggesting a potential adjunctive therapy for intestinal fi brosis. IM could consequently reduce fi brosis in DSS colitis by direct or indirect effect on profi brogenic factors or fi broblasts. Therefore, the precise effect of IM on intestinal fi brosis should be investigated further.

Original languageEnglish (US)
Pages (from-to)140-151
Number of pages12
JournalMedical Molecular Morphology
Volume45
Issue number3
DOIs
StatePublished - Jun 2012

Keywords

  • Crohn's disease
  • Fibrosis
  • Infl ammatory bowel disease
  • Irsogladine maleate
  • Mesenchymal cells
  • TGF-®

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology

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