MicroRNA-126 Deficiency Affects the Development of Thymus CD4+ Single-Positive Cells through Elevating IRS-1
MicroRNA-126 Deficiency Affects the Development of Thymus CD4+ Single-Positive Cells through Elevating IRS-1
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DOI：
10.1159/000490710
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发表时间：
2018-07
影响因子：
2.8
通讯作者：
Lin Hu;Hualin Xu;Jia Lu;Ya Zhou;Fengyun Chu;Wen Zheng;Liangyu Lei;Juanjuan Zhao;Hairong Wang;Mengmeng Guo;Chao Chen;Lin Xu
中科院分区：
文献类型：
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作者：
Lin Hu;Hualin Xu;Jia Lu;Ya Zhou;Fengyun Chu;Wen Zheng;Liangyu Lei;Juanjuan Zhao;Hairong Wang;Mengmeng Guo;Chao Chen;Lin Xu
背景：microRNA-126(miR-126)是一个独特的miRNA家族成员，据报道参与了某些类型免疫细胞的发育和功能。然而，miR-126在CD4+T细胞发育中的潜在作用仍有待阐明。目的：探讨miR-126在胸腺CD4+T细胞发育中的作用及其意义。方法：采用实时荧光定量聚合酶链式反应(Real-time PCR)检测胸腺CD4+单阳性(SP)细胞miR-126的相对表达水平。用组织病理学方法评估胸腺组织可能的变化。用流式细胞仪检测胸腺细胞总数和活化相关分子CD62L、CD69、CD44以及增殖相关核抗原Ki-67的表达。流式细胞仪检测IRS-1的表达及Akt、Erk等相关信号转导通路。结果：与野生型(WT)小鼠相比，miR-126基因敲除(KD)小鼠胸腺细胞总数显著增加。此外，在miR-126KD小鼠中，胸腺CD4+SP细胞的比例和绝对细胞数显著减少。进一步分析表明，活化相关分子CD62L、CD69和CD44以及增殖相关核抗原Ki-67在CD4+SP细胞中的频率也发生了显著变化。在机制方面，miR-126KD小鼠的CD4+SP细胞中IRS-1的表达水平显著升高。此外，信号分子磷酸化(P)-Akt和p-Erk的表达水平也发生了显著变化。结论：我们的工作首次揭示了miR-126在胸腺中CD4+SP细胞发育中的未知作用，这可能最终有助于胸腺细胞发育的研究。
Background: MicroRNA-126 (miR-126), a distinct miRNA family member, has been reported to be involved in the development and function of some types of immune cells. However, the potential role of miR-126 in the development of CD4+ T cells remains to be elucidated. Objectives: To investigate the potential role of miR-126 in the development of CD4+ T cells in the thymus and explore its significance. Methods: The relative expression level of miR-126 in thymus CD4+ single-positive (SP) cells was detected by Real-Time PCR assay. The possible change in thymus tissue was assessed by histopathology. The total cell number of thymocytes and the expression of activation-associated molecules including CD62L, CD69, and CD44, as well as proliferation-associated nuclear antigen Ki-67, in CD4+ SP cells were assessed by flow cytometric analysis. The expression of IRS-1 and related signaling pathways including Akt and Erk were determined by flow cytometric analysis. Results: Compared with that in wild-type (WT) mice, the total cell number of thymocytes in miR-126 knockdown (KD) mice increased significantly. Moreover, the proportion and absolute cell number of thymic CD4+ SP cells decreased significantly in miR-126 KD mice. Further analysis showed that the frequencies of activation-associated molecules including CD62L, CD69, and CD44, as well as proliferation-associated nuclear antigen Ki-67 in CD4+ SP cells also changed significantly, respectively. Mechanism aspect, the expression level of IRS-1, a putative target of miR-126, increased significantly in CD4+ SP cells in miR-126 KD mice. Moreover, the expression levels of the signaling molecules phosphorylated (p)-Akt and p-Erk also changed significantly. Conclusions: Our work is the first to reveal a previously unknown role of miR-126 in the development of CD4+ SP cells in the thymus, which might ultimately benefit studies on development of thymocytes.