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Medical Molecular Morphology

, Volume 45, Issue 3, pp 140–151 | Cite as

Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulfate sodium

  • Hana Yamaguchi
  • Kenji SuzukiEmail author
  • 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
Original Paper

Abstract

Intestinal fibrosis is a common and severe complication of inflammatory bowel disease (IBD), especially Crohn’s disease (CD). To investigate the therapeutic approach to intestinal fibrosis, we have developed a mouse model of intestinal fibrosis 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 profibrogenic mesenchymal cells such as fibroblasts (vimentin+, α-SMA) and myofibroblasts (vimentin+, α-SMA+) in both mucosa and submucosa of the colon with infiltrating inflammatory cells, and increased mRNA expressions of collagen type I, transforming growth factor (TGF)-β, 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 significantly decreased or suppressed, suggesting a potential adjunctive therapy for intestinal fibrosis. IM could consequently reduce fibrosis in DSS colitis by direct or indirect effect on profibrogenic factors or fibroblasts. Therefore, the precise effect of IM on intestinal fibrosis should be investigated further.

Key words

Irsogladine maleate Inflammatory bowel disease Crohn’s disease Fibrosis Mesenchymal cells TGF-β 

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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2012

Authors and Affiliations

  • Hana Yamaguchi
    • 1
    • 2
  • Kenji Suzuki
    • 1
    • 3
    Email author
  • Masaki Nagata
    • 2
  • Tomoyuki Kawase
    • 4
  • Vijayakumar Sukumaran
    • 5
  • Rajarajan A. Thandavarayan
    • 5
  • Yusuke Kawauchi
    • 1
  • Junji Yokoyama
    • 1
  • Masayuki Tomita
    • 6
  • Hiroshi Kawachi
    • 6
  • Kenichi Watanabe
    • 5
  • Hiroyuki Yoneyama
    • 7
  • Hitoshi Asakura
    • 1
  • Ritsuo Takagi
    • 2
  1. 1.Departments of Gastroenterology and HepatologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  2. 2.Department of Oral and Maxillofacial SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  3. 3.Department of Medicine (III)Niigata University Medical and Dental HospitalNiigataJapan
  4. 4.Department of Oral BioengineeringNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  5. 5.Department of Clinical Pharmacology, Faculty of Pharmaceutical SciencesNiigata University of Pharmacy and Applied Life SciencesNiigataJapan
  6. 6.Department of Cell Biology, Institute of NephrologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  7. 7.Stelic Institute of Regenerative MedicineStelic Institute & Co.TokyoJapan

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