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Gut. 2014 Dec;63(12):1902-12. doi: 10.1136/gutjnl-2013-305632. Epub 2014 Feb 17.

Involvement of interleukin-17A-induced expression of heat shock protein 47 in intestinal fibrosis in Crohn's disease.

Author information

1
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
2
Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
3
Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
4
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan.
5
Laboratory of Molecular and Cellular Biology, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Kyoto, Japan.

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.

KEYWORDS:

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

PMID:
24534724
DOI:
10.1136/gutjnl-2013-305632
[Indexed for MEDLINE]
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