MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjogren's syndrome

被引:102
作者
Chen, Ji-Qing [1 ]
Papp, Gabor [1 ]
Poliska, Szilard [2 ]
Szabo, Krisztina [1 ]
Tarr, Tunde [1 ]
Balint, Balint Laszlo [2 ]
Szodoray, Peter [3 ,4 ]
Zeher, Margit [1 ]
机构
[1] Univ Debrecen, Fac Med, Div Clin Immunol, Debrecen, Hungary
[2] Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, Genom Med & Bioinformat Core Facil, Debrecen, Hungary
[3] Univ Oslo, Oslo Univ Hosp, Rikshosp, Ctr Immune Regulat, Oslo, Norway
[4] Univ Oslo, Oslo Univ Hosp, Rikshosp, Dept Immunol, Oslo, Norway
关键词
B-CELL SUBSETS; CLASSIFICATION CRITERIA; SIGNALING PROTEINS; MIRNAS; RNA; AUTOIMMUNITY; BIOGENESIS; COMPONENT; SIRNAS; GENE;
D O I
10.1371/journal.pone.0174585
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-1505p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.
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页数:14
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