title: Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease.
abstract: OBJECTIVE
  Intestinal fibrosis is a clinically important issue in Crohn's disease (CD). Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone involved in fibrotic diseases. The molecular mechanisms of HSP47 induction in intestinal fibrosis related to CD, however, remain unclear. Here we investigated the role of interleukin (IL)-17A-induced HSP47 expression in intestinal fibrosis in CD.
  
  
  METHODS
  Expressions of HSP47 and IL-17A in the intestinal tissues of patients with IBD were determined. HSP47 and collagen I expressions were assessed in intestinal subepithelial myofibroblasts (ISEMFs) isolated from patients with IBD and CCD-18Co cells treated with IL-17A. We examined the role of HSP47 in IL-17A-induced collagen I expression by administration of short hairpin RNA (shRNA) to HSP47 and investigated signalling pathways of IL-17A-induced HSP47 expression using specific inhibitors in CCD-18Co cells.
  
  
  RESULTS
  Gene expressions of HSP47 and IL-17A were significantly elevated in the intestinal tissues of patients with active CD. Immunohistochemistry revealed HSP47 was expressed in α-smooth muscle actin (α-SMA)-positive cells and the number of HSP47-positive cells was significantly increased in the intestinal tissues of patients with active CD. IL-17A enhanced HSP47 and collagen I expressions in ISEMFs and CCD-18Co cells. Knockdown of HSP47 in these cells resulted in the inhibition of IL-17A-induced collagen I expression, and analysis of IL-17A signalling pathways revealed the involvement of c-Jun N-terminal kinase in IL-17A-induced HSP47 expression.
  
  
  CONCLUSIONS
  IL-17A-induced HSP47 expression is involved in collagen I expression in ISEMFs, which might contribute to intestinal fibrosis in CD.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Honzawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shiokawa
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Hirotsugu
authors.identifier: http://orcid.org/0000-0003-1552-7799
authors.initials: H
authors.lastname: Imaeda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsuura
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ikeuchi
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000328:Adult; D000368:Aged; D024042:Collagen Type I / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000378:metabolism*; D020869:Gene Expression Profiling; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology
chemical_list: D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D020381:Interleukin-17
keywords: Crohn's disease (CD); Fibrosis; Heat shock protein (HSP); Myofibroblasts