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IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT

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Abstract

Background

Intestinal fibrosis is a common complication of Crohn’s disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial–mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported.

Aims

To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT.

Methods

In this study, we evaluated the expression of IL-17A and EMT-related genes in colonic mucosal biopsy tissues of CD patients and control individuals. Then, we examined the changes of EMT-related genes and fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing concentrations of IL-17A or with TGF-β1, to verify the potential inductive effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo.

Results

We found the occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CD patients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal epithelial cells that come with reduced E-cadherin expression and increased expression of vimentin, snail, and α-SMA. We further found that anti-IL-17A treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine.

Conclusions

Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.

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Acknowledgments

This work was supported by Liaoning Province Science and Technology Project (2013225049). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Endoscopy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China

    Hui-Jing Zhang, Yi-Ning Zhang, Huan Zhou, Lin Guan, Yue Li & Ming-Jun Sun

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Contributions

MJ-S was involved in conception and design, interpretation of data, and manuscript revision. HJ-Z, YN-Z, and HZ performed the experiments. LG and YL collected the biopsy samples. HJ-Z YN-Z analyzed the data. MJ-S contributed reagents/materials/analysis tools. HJ-Z and YN-Z wrote the paper. All authors approved the final version of the manuscript.

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Correspondence to Ming-Jun Sun.

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All authors do not have a commercial or other association that might pose a conflict of interest.

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Zhang, HJ., Zhang, YN., Zhou, H. et al. IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT. Dig Dis Sci 63, 2898–2909 (2018). https://doi.org/10.1007/s10620-018-5234-x

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  • DOI: https://doi.org/10.1007/s10620-018-5234-x

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