TY - JOUR
T1 - Irsogladine maleate ameliorates infl ammation and fi brosis in mice with chronic colitis induced by dextran sulfate sodium
AU - Yamaguchi, Hana
AU - Suzuki, Kenji
AU - Nagata, Masaki
AU - Kawase, Tomoyuki
AU - Sukumaran, Vijayakumar
AU - Thandavarayan, Rajarajan A.
AU - Kawauchi, Yusuke
AU - Yokoyama, Junji
AU - Tomita, Masayuki
AU - Kawachi, Hiroshi
AU - Watanabe, Kenichi
AU - Yoneyama, Hiroyuki
AU - Asakura, Hitoshi
AU - Takagi, Ritsuo
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Crohn's disease
KW - Fibrosis
KW - Infl ammatory bowel disease
KW - Irsogladine maleate
KW - Mesenchymal cells
KW - TGF-®
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U2 - 10.1007/s00795-011-0550-7
DO - 10.1007/s00795-011-0550-7
M3 - Article
C2 - 23001296
AN - SCOPUS:84871410101
SN - 1860-1480
VL - 45
SP - 140
EP - 151
JO - Medical Molecular Morphology
JF - Medical Molecular Morphology
IS - 3
ER -