title: Analysis of intestinal fibrosis in chronic colitis in mice induced by dextran sulfate sodium.
abstract: Fibrogenic mesenchymal cells including fibroblasts and myofibroblasts play a key role in intestinal fibrosis, however, their precise role is largely unknown. To investigate their role in intestinal fibrosis, we analyzed the lesions of chronic colitis in C57BL/6 (B6) mice induced by dextran sulfate sodium (DSS). B6 mice exposed to single cycle administration of DSS for 5 days developed acute colitis that progressed to severe chronic inflammation with dense infiltrates of mononuclear cells, irregular epithelial structure, thickening of colonic wall, and persistent deposits of collagen. Increased mRNA expressions of proinflammatory cytokines are correlated with extensive cellular infiltration, and the mRNA expressions of collagen 1, transforming growth factor (TGF)-β, and matrix metalloproteinases were also enhanced in the colon. In the colon of chronic DSS colitis, fibroblasts (vimentin(+), α-smooth muscle actin (α-SMA)(-)) were increased in both mucosal and submucosal layers, while myofibroblasts (vimentin(+), α-SMA(+)) were increased in mucosal but not in submucosal layers. Primary mouse subcutaneous fibroblast cultures experiments revealed that exogenously added TGF-β 1 substantially augmented the expressions of both vimentin and α-SMA proteins with increased production of collagen. In conclusion, profibrogenic mesenchymal cells play an important role in the development of intestinal fibrosis in this chronic DSS-induced colitis model.
authors.affiliation: Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City, Niigata, Japan. kjsuzuki@med.niigata-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Sun
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawase
authors.forename: Hana
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Sukumaran
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawauchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nishino
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Asakura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D003094:Collagen; D016264:Dextran Sulfate