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Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease
  1. Yusuke Honzawa1,
  2. Hiroshi Nakase1,
  3. Masahiro Shiokawa1,
  4. Takuya Yoshino1,
  5. Hirotsugu Imaeda2,
  6. Minoru Matsuura1,
  7. Yuzo Kodama1,
  8. Hiroki Ikeuchi3,
  9. Akira Andoh2,
  10. Yoshiharu Sakai4,
  11. Kazuhiro Nagata5,
  12. Tsutomu Chiba1
  1. 1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan
  2. 2Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
  3. 3Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
  4. 4Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan
  5. 5Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Kyoto, Japan
  1. Correspondence to Dr Hiroshi Nakase, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; hiropy_n{at}kuhp.kyoto-u.ac.jp

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.

Design 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.

  • Fibrosis
  • Crohn's disease (CD)
  • Heat shock protein (HSP)
  • Myofibroblasts

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