MicroRNA Expression in Cutaneous Lupus: A New Window to Understand Its Pathogenesis

MicroRNA Expression in Cutaneous Lupus: A New Window to Understand Its Pathogenesis
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DOI:
10.1155/2019/5049245
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发表时间:
2019-12-30
影响因子:
4.6
通讯作者:
Zuniga, Joaquin
Zuniga, Joaquin
中科院分区:
医学3区
文献类型:
--
作者:
Mendez-Flores, Silvia;Furuzawa-Carballeda, Janette;Zuniga, Joaquin

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背景资料。关于miRNAs在皮肤性狼疮发病机制中的作用还没有研究。目标。它是为了评估一组选定的循环miRNAs的水平,这些miRNAs可能参与调节皮肤狼疮的免疫反应、炎症和纤维化。方法:研究方法。这是一项横断面研究。其中亚急性(SCLE)患者22例,盘状病变(DLE)患者20例,健康献血者(HD)19例。采用定量逆转录聚合酶链式反应(QRT-PCR)、外周血流式细胞术、皮肤免疫组织化学等方法检测外周血中CD4T细胞和调节细胞的分布及其与循环miRNAs的相关性。结果。与HD相比,SCLE患者的miR-150、miR-1246、miR-21、miR-23b和miR-146水平下调。与HD相比,DLE患者的miR-150、miR-1246和miR-21水平下调。CD123(+)/CD196(+)/IDO+细胞与miR-150呈正相关,CD123(+)/CD196(+)/IDO+细胞与miR-150呈正相关。在组织中,CD20(+)/IL-10(+)细胞与miR-21、CD20(+)/IL-10(+)细胞与miR-31呈正相关,CD20(+)/IL-10(+)细胞与miR-1246、miR-146a呈正相关。在SCLE中,miR-150水平较低与Clasi评分较高相关。KEGG途径丰富分析表明,miR-21、miR-31、miR-23b、miR-146a、miR-1246和miR-150共有细胞周期调控通路、p53、转化生长因子-β、甲状腺激素和癌症信号通路。结论。与HD相比,两个CLE品种的miR-150、miR-1246和miR-21的下调被确定。
Background. The role of miRNAs in the pathogenesis of cutaneous lupus has not been studied. Objective. It was to assess the levels of a selected panel of circulating miRNAs that could be involved in the regulation of the immune response, inflammation, and fibrosis in cutaneous lupus. Methods. It was a cross-sectional study. We included 22 patients with subacute (SCLE) and 20 with discoid (DLE) lesions, and 19 healthy donors (HD). qRT-PCR for miRNA analysis, flow cytometry in peripheral blood, and skin immunohistochemistry were performed to determine the distribution of CD4 T cells and regulatory cells and their correlation with circulating miRNAs. Results. miR-150, miR-1246, miR-21, miR-23b, and miR-146 levels were downregulated in SCLE vs. HD. miR-150, miR-1246, and miR-21 levels were downregulated in DLE vs. HD. Peripheral CD4(+)/CD25(-)/IL-4(+) cells and CD4(+)/CD25(hi)/Foxp3(+) were negatively associated with miR-23b, and CD4(+)/CD25(-)/IFN-gamma(+) with miR-1246 in SCLE, whereas CD123(+)/CD196(+)/IDO+ cells were positively associated with miR-150 in DLE. In the tissue, CD4(+)/IL-4(+) and CD20(+)/IL-10(+) cells were positively associated with miR-21 and CD4(+)/IFN-gamma(+) with miR-31 in SCLE, whereas CD4(+)/IL-4(+) cells were positively associated with miR-150, and CD20(+)/IL-10(+) cells with miR-1246 and miR-146a in DLE. In the SCLE, lower miR-150 levels were correlated with higher CLASI scores. The KEGG pathway enrichment analysis revealed that cell cycle regulation pathways, p53, TGF-beta, thyroid hormone, and cancer signaling pathways were shared between miR-21, miR-31, miR-23b, miR-146a, miR-1246, and miR-150. Conclusions. A downregulation of miR-150, miR-1246, and miR-21 in both CLE varieties vs. HD was determined.