Author:
Chang Rui,Yi Shenglan,Tan Xiao,Huang Yang,Wang Qingfeng,Su Guannan,Zhou Chunjiang,Cao Qingfeng,Yuan Gangxiang,Kijlstra Aize,Yang Peizeng
Abstract
AimTo elucidate the role of microRNA-20a-5p (miR-20a-5p) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.MethodsQuantitative 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.ResultsThe 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.ConclusionsOur 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.
Funder
Chongqing Key Laboratory of Ophthalmology
National Key R&D Program of China
Natural Science Major International (Regional) Joint Research Project
National Natural Science Foundation Project
National Key Clinical Specialties Construction Program of China, Chongqing Science & Technology Platform and Base Construction Program
Subject
Cellular and Molecular Neuroscience,Sensory Systems,Ophthalmology
Cited by
29 articles.
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