Increased let-7b-5p is associated with enhanced BAFF-R expression and B cell survival in immune thrombocytopenia.
Increased let-7b-5p is associated with enhanced BAFF-R expression and B cell survival in immune thrombocytopenia.
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let-7b-5p 增加与免疫性血小板减少症中 BAFF-R 表达增强和 B 细胞存活相关。
DOI：
10.1016/j.intimp.2021.107393
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发表时间：
2021-01
影响因子：
5.6
通讯作者：
He Yang
中科院分区：
文献类型：
--
作者：
Wang Yao;Jia Xi;Zhou Ling;Yin Jie;Zhao Yunxiao;Dai Lan;Zuo Bin;He Yang
研究背景B细胞通过产生血小板自身抗体在免疫性血小板减少症（ITP）的发病机制中起重要作用。越来越多的证据表明microRNA（miRNA）是B细胞中的关键调节因子。在ITP中miRNA对B细胞功能障碍的贡献尚未被描述。本研究旨在检测ITP患者外周血B细胞中let-7 B-5 p的表达，探讨其与ITP患者B细胞功能的关系。细胞计数法检测B细胞存活率。通过定量PCR对let-7 b-5 p的水平进行定量。流式细胞仪检测细胞表面B细胞活化因子受体（BAFF-R）的表达。let-7 B-5 p的作用在分离的B细胞中通过转染miRNA模拟物或抑制剂来检测。结果显示，与健康对照相比，ITP患者B细胞中let-7 B-5 p升高，B细胞存活增强。BAFF和B细胞受体刺激可诱导let-7 B-5 pin的表达。let-7 B-5 p在B细胞中的过表达增强了表面BAFF-R的表达，促进了B细胞的存活。结论let-7 b-5 p是一种促进B细胞生存的miRNA，let-7 b-5 p表达增加与ITP患者B细胞表面BAFF-R增强有关。
BackgroundB cells play a key role in the pathogenesis of immune thrombocytopenia (ITP) by producing platelet autoantibodies. Accumulating evidence suggest that microRNA (miRNA) is a critical regulator in B cells. The contribution of miRNA to B cell dysfunction in ITP has not been described. The aim of this study was to examine the expression of miRNA let-7b-5p in B cells of ITP patients and investigate its possible association with B cell function in ITP.MethodsThe CD19+cells were isolated from peripheral mononuclear cells of ITP patients and healthy controls using immunomagnetic microbeads. B cell survivalin vitrowas evaluated by cell counting. The level of let-7b-5p was quantified by quantitative PCR. The surface expression of B cell activating factor receptor (BAFF-R) was detected by flow cytometry. The role of let-7b-5p was examined in isolated B cells by transfecting miRNA mimics or inhibitors.ResultsThe results showed that let-7b-5p in B cells was elevated, and B cell survival was enhanced in ITP patients compared with healthy controls. BAFF and B cell receptor stimulation can induce the expression of let-7b-5pin vitro. Overexpression of let-7b-5p in B cells enhanced the expression of surface BAFF-R and promoted B cell survival. Moreover, let-7b-5p enhanced the phosphorylation of NF-κB2 p100 and upregulated the expression of survival factor Bcl-xL after BAFF induction.ConclusionLet-7b-5p is a pro-survival miRNA in B cells and increased let-7b-5p is associated with enhanced surface BAFF-R in ITP.
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