Unraveling natalizumab effects on deregulated miR-17 expression in CD4+ T cells of patients with relapsing-remitting multiple sclerosis.
Unraveling natalizumab effects on deregulated miR-17 expression in CD4+ T cells of patients with relapsing-remitting multiple sclerosis.
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DOI：
10.1155/2014/897249
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发表时间：
2014
影响因子：
4.1
通讯作者：
Lindberg RL
中科院分区：
文献类型：
--
作者：
Meira M;Sievers C;Hoffmann F;Rasenack M;Kuhle J;Derfuss T;Kappos L;Lindberg RL
MicroRNAs(MiRNAs)是一个非编码RNA家族，在基因表达的转录后调控中发挥关键作用。越来越多的证据支持它们参与多发性硬化症(MS)的发病机制。在这里，我们比较了接受那他珠单抗治疗的复发缓解(RR)MS患者和未治疗患者的CD4+T细胞中miR-17的表达。在那他珠单抗治疗下，miR-17表达下调，在复发时上调，因此支持miR-17在MS免疫发病机制中的可能作用。MiR-17的下调与PTEN、BIM、E2F1和p21靶基因的上调有关。在体外，miR-17的抑制与相同靶点的上调有关，并导致CD4+T细胞的激活和增殖受损。我们进一步描述了未经治疗的患者和健康志愿者(HV)中TGFBR2表达的解除调节，并在体外证实了miR-17和TGFBR2表达之间的联系。这些发现支持了Natalizumab对特定miRNA表达的影响，以及随后参与细胞增殖和细胞周期控制的基因的表达。
MicroRNAs (miRNAs) are a family of noncoding RNAs that play critical roles in the posttranscriptional regulation of gene expression. Accumulating evidence supports their involvement in the pathogenesis of multiple sclerosis (MS). Here, we compare miR-17 expressions in CD4+ T cells from relapsing-remitting (RR) MS patients treated with natalizumab versus untreated patients. miR-17 was downregulated under natalizumab treatment and upregulated during relapse, therefore supporting a possible role of miR-17 in MS immunopathogenesis. Downregulation of miR-17 was associated with upregulation of PTEN, BIM, E2F1, and p21 target genes. In vitro miR-17 inhibition was associated with upregulation of the same targets and resulted in impaired CD4+ T cell activation and proliferation. We further describe deregulated TGFBR2 expression in untreated patients versus healthy volunteers (HVs) and confirm in vitro the link between miR-17 and TGFBR2 expressions. These findings support an effect of natalizumab on expression of specific miRNA and subsequent expression of genes involved in proliferation and control of the cell cycle.
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