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Ets-1 和 miR-326 在系统性红斑狼疮患者 CD19B 细胞发病机制中的潜在作用。

The potential role of Ets-1 and miR-326 in CD19B cells in the pathogenesis of patients with systemic lupus erythematosus.

机构信息

Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, No.17 Lu Jiang Road, Hefei, 230001, China.

Centre for Transplantation and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Camperdown, NSW, Australia.

出版信息

Clin Rheumatol. 2019 Apr;38(4):1031-1038. doi: 10.1007/s10067-018-4371-0. Epub 2018 Nov 19.

Abstract

OBJECTIVES

The aim of this study was to investigate the B cell-associated transcription factors, Ets-1 and microRNA, miR-326 in systemic lupus erythematosus (SLE) patients, and their correlation with the pathogenesis of SLE.

METHOD

A total of 44 SLE patients and 20 healthy controls were enrolled in this research, all patients fulfilled the American College of Rheumatology classification criteria for SLE. The mRNA expression of Ets-1 and miR-326 in CD19B cells from SLE patients were examined by qRT-PCR. The percentages of CD19CD138plasma cells were analyzed by Flow cytometry.

RESULTS

We found decreased expression of Ets-1 mRNA in SLE patients compared with the healthy controls ([0.228 (0.145, 0.507)] vs [0.583 (0.452, 0.763)], p = 0.001),while increased expression of miR-326 mRNA in CD19B cells SLE patients compared with the healthy controls([1.092 (0.457, 2.855)] vs [0.685 (0.274, 0.819)], p = 0.008). The percentage of CD19CD138plasma cells in SLE patients was higher than that of healthy controls (0.55 ± 0.21% vs 0.36 ± 0.21%, p = 0.002). Moreover, a negative correlation between expression of Ets-1 mRNA and miR-326 mRNA in CD19B cells was detected (r = - 0.334, p = 0.027). A significant association between the occurrences of CD19CD138plasma cells and the levels of Ets-1 mRNA and miR-326 mRNA was observed (r = - 0.417, p = 0.005 and r = 0.482, p = 0.001, respectively).

CONCLUSIONS

Our results suggest that miR-326 might promote B cells differentiation by targeting Ets-1, a negative regulator of B cells differentiation and therefore participate in the pathogenesis of SLE.

摘要

目的

本研究旨在探讨系统性红斑狼疮(SLE)患者中 B 细胞相关转录因子 Ets-1 和 microRNA,miR-326 的表达情况及其与 SLE 发病机制的关系。

方法

本研究共纳入 44 例 SLE 患者和 20 例健康对照者,所有患者均符合美国风湿病学会 SLE 分类标准。采用 qRT-PCR 检测 SLE 患者 CD19B 细胞中 Ets-1 和 miR-326 的 mRNA 表达水平,采用流式细胞术分析 CD19CD138 浆细胞的百分比。

结果

与健康对照组相比,SLE 患者 Ets-1 mRNA 的表达水平降低[0.228(0.145,0.507)]vs[0.583(0.452,0.763)],p=0.001],而 CD19B 细胞中 miR-326 mRNA 的表达水平升高[1.092(0.457,2.855)]vs[0.685(0.274,0.819)],p=0.008]。SLE 患者 CD19CD138 浆细胞的百分比高于健康对照组(0.55±0.21% vs 0.36±0.21%,p=0.002)。此外,我们还检测到 CD19B 细胞中 Ets-1 mRNA 和 miR-326 mRNA 的表达呈负相关(r=-0.334,p=0.027)。CD19CD138 浆细胞的出现与 Ets-1 mRNA 和 miR-326 mRNA 的水平之间存在显著的相关性(r=-0.417,p=0.005 和 r=-0.482,p=0.001)。

结论

我们的研究结果表明,miR-326 可能通过靶向 Ets-1 促进 B 细胞分化,Ets-1 是 B 细胞分化的负调节因子,因此参与了 SLE 的发病机制。

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