You are here

Article Text

Article menu

Download PDFPDF

Laboratory science
MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt-Koyanagi-Harada disease
  1. Rui Chang1,
  2. Shenglan Yi1,
  3. Xiao Tan1,
  4. Yang Huang1,
  5. Qingfeng Wang1,
  6. Guannan Su1,
  7. Chunjiang Zhou1,
  8. Qingfeng Cao1,
  9. Gangxiang Yuan1,
  10. Aize Kijlstra2,
  11. Peizeng Yang1
  1. 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, China
  2. 2 University Eye Clinic Maastricht, Maastricht, The Netherlands
  1. Correspondence to Dr Peizeng Yang, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, China; peizengycmu{at}126.com

Abstract

Aim To elucidate the role of microRNA-20a-5p (miR-20a-5p) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

Methods Quantitative real-time PCR was used to quantify miR-20a-5p expression in CD4+ T cells from patients with active VKH and normal controls. The promoter methylation status of miR-20a-5p was detected by bisulfite sequencing PCR. Targets were evaluated by a luciferase reporter assay. The functional effects of miR-20a-5p on CD4+ T cells from patients with active VKH were assessed by upregulation or downregulation of its expression using liposomes.

Results The miR-20a-5p level was significantly decreased in CD4+ T cells from patients with active VKH as compared with normal controls. The two genes, oncostatin M (OSM) and C-C motif chemokine ligand 1 (CCL1), were identified as targets of miR-20a-5p. The upregulation of miR-20a-5p significantly suppressed interleukin 17 (IL-17) production in CD4+ T cells from patients with active VKH, whereas downregulation of miR-20a-5p exhibited an inverse effect. In addition, overexpression of OSM and CCL1 could rescue the effect of the upregulation of miR-20a-5p. Moreover, the level of miR-20a-5p was reduced in response to hypermethylation of the promoter. Further study showed that miR-20a-5p suppressed the activity of the phosphoinositide 3-kinase-AKT pathway.

Conclusions Our findings indicate that downregulation of miR-20a-5p is caused by promoter hypermethylation. MiR-20a-5p could also suppress the production of IL-17 by targeting OSM and CCL1 production in CD4+ T cells in patients with active VKH.

  • experimental laboratory
  • immunology
  • inflammation

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bjophthalmol-2017-311079

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors RC, PY: conceived the idea and designed the experiments. CZ, QC: sample collection. RC, SY, QW: performed all the experiments. GY: flow cytometry test. RC, YH: analysed the data. RC, XT: wrote the manuscript. PY, GS, AK: revised the manuscript.

    • Funding This work was supported by National Key R&D Program of China (grant no 2016YFC0904000), Natural Science Major International (Regional) Joint Research Project (grant no 81320108009), National Natural Science Foundation Project (grant no 31370893), Chongqing Key Laboratory of Ophthalmology (grant no CSTC, 2008CA5003), National Key Clinical Specialties Construction Program of China, Chongqing Science & Technology Platform and Base Construction Program (grant no cstc2014pt-sy10002) and National Natural Science Foundation Project (grant no 81400390).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval The study was approved by the ethical committee of Chongqing Medical University. The tenets of the Declaration of Helsinki were followed during all procedures of the present study.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    Linked Articles

    • At a glance
      Highlights from this issue
      Keith Barton James Chodosh Jost B Jonas
      British Journal of Ophthalmology 2018; 102 i-ii Published Online First: 24 Jan 2018. doi: 10.1136/bjophthalmol-2018-311851