Identification of differently expressed mRNAs by peripheral blood mononuclear cells in Vogt-Koyanagi-Harada disease

作者全名："Li, Yujing; Su, Guannan; Huang, Fanfan; Zhu, Ying; Luo, Xiang; Kijlstra, Aize; Yang, Peizeng"

作者地址："[Li, Yujing; Su, Guannan; Huang, Fanfan; Zhu, Ying; Luo, Xiang; Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing 400016, Peoples R China; [Kijlstra, Aize] Univ Eye Clin Maastricht, NL-6211 Maastricht, Netherlands"

通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000831198700025

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：5

开始页：1378

结束页：1388

文献类型：Article

关键词：Vogt-Koyanagi-Harada disease; uveitis; mRNA sequencing; Peripheral blood mononuclear cells

摘要："Vogt-Koyanagi-Harada disease (VKH) is a rare autoimmune disease characterized by diffuse and bilateral uveitis, alopecia, tinnitus, hearing loss, vitiligo and headache. The tran-scriptional expression pattern of peripheral blood mononuclear cells (PBMC) in VKH remains largely unknown. In this study, mRNA sequencing was conducted in PBMC from VKH patients with active uveitis before treatment (n = 7), the same patients after prednisone combined with cyclosporine treatment (n = 7) and healthy control subjects strictly matched with gender and age (n = 7). We found 118 differentially expressed genes (DEGs) between VKH patients and healthy control subjects, and 21 DEGs between VKH patients before and after treatment. TRIB1 was selected as a potential biomarker to monitor the development of VKH according to the mRNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to predict the possible biological functions and signaling path-ways of DEGs. Neutrophil degranulation, peptidase regulator activity, secretory granule mem-brane, cellular response to peptide, growth factor binding and cell projection membrane were enriched as GO annotations of DEGs. Arachidonic acid metabolism and mitogen-activated pro-tein kinase (MAPK) signaling pathway were potential signaling pathways involved in pathogen-esis and drug response of VKH. A protein-protein interaction (PPI) network was constructed by STRING, and colony stimulating factor 1 receptor (CSF1R) was identified as the hubgene of all DEGs by Cytoscape. The cell type presumed to contribute to the aberrant expression of DEGs was analyzed with the use of publicly available single-cell sequencing data of PBMC from a healthy donor and single-cell sequencing dataset of monocytes from VKH patients. Our findings may help to decipher the underlying cellular and molecular pathogenesis of VKH and may lead novel therapeutic applications."

基金机构："National Natural Science Foundation Key Program, China [81930023]; Natural Science Foundation Major International (Regional) Joint Research Project, China [81720108009]; Chongqing Outstanding Scientists Project (2019); Chongqing Key Laboratory of Ophthalmology, China [2008CA5003]; Chongqing Science & Technology Platform and Base Construction Program, China [cstc2014pt-sy10002]; Chongqing Chief Medical Scientist Project, China (2018)"

基金资助正文："This study was financially supported by National Natural Science Foundation Key Program, China (No. 81930023) , Natural Science Foundation Major International (Regional) Joint Research Project, China (No. 81720108009) , Chongqing Outstanding Scientists Project (2019) , Chongqing Key Laboratory of Ophthalmology, China (No. CSTC, 2008CA5003) , Chongqing Science & Technology Platform and Base Construction Program, China (No. cstc2014pt-sy10002) and the Chongqing Chief Medical Scientist Project, China (2018) ."