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

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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.

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Authors and Affiliations

  1. Departments of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Hana Yamaguchi, Kenji Suzuki, Yusuke Kawauchi, Junji Yokoyama & Hitoshi Asakura

  2. Department of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Hana Yamaguchi, Masaki Nagata & Ritsuo Takagi

  3. Department of Medicine (III), Niigata University Medical and Dental Hospital, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8122, Japan

    Kenji Suzuki

  4. Department of Oral Bioengineering, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Tomoyuki Kawase

  5. Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan

    Vijayakumar Sukumaran, Rajarajan A. Thandavarayan & Kenichi Watanabe

  6. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Masayuki Tomita & Hiroshi Kawachi

  7. Stelic Institute of Regenerative Medicine, Stelic Institute & Co., Tokyo, Japan

    Hiroyuki Yoneyama

Authors
  1. Hana Yamaguchi
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  2. Kenji Suzuki
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  3. Masaki Nagata
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  4. Tomoyuki Kawase
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  14. Ritsuo Takagi
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Correspondence to Kenji Suzuki.

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Yamaguchi, H., Suzuki, K., Nagata, M. et al. Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulfate sodium. Med Mol Morphol 45, 140–151 (2012). https://doi.org/10.1007/s00795-011-0550-7

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  • DOI: https://doi.org/10.1007/s00795-011-0550-7

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