MiR-142-3p attenuates the migration of CD4⁺ T cells through regulating actin cytoskeleton via RAC1 and ROCK2 in arteriosclerosis obliterans.
MiR-142-3p attenuates the migration of CD4⁺ T cells through regulating actin cytoskeleton via RAC1 and ROCK2 in arteriosclerosis obliterans.
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DOI：
10.1371/journal.pone.0095514
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Liu J;Li W;Wang S;Wu Y;Li Z;Wang W;Liu R;Ou J;Zhang C;Wang S
CD 4 + T细胞的迁移在动脉硬化闭塞症（arteriosclerosis obliterans，阿索）中起重要作用。然而，涉及CD 4 + T细胞迁移的分子机制仍不清楚。本研究旨在检测miR-142- 3 p在阿索患者CD 4 + T细胞中的表达变化，探讨其在CD 4 + T细胞迁移中的作用及其可能机制。我们通过qRT-PCR和原位杂交检测发现，阿索患者CD 4 + T细胞中miR-142- 3 p的表达显著下调。趋化因子（C-X-C motif）配体12（CXCL 12）是阿索条件下常见的炎性趋化因子，能够下调培养的CD 4 + T细胞中miR-142- 3 p的表达。通过慢病毒介导的基因转移上调miR-142- 3 p对体外培养的人细胞和体内小鼠脾脏和脾脏中的CD 4 + T细胞迁移具有强烈的抑制作用。RAC 1和ROCK 2被鉴定为人CD 4 + T细胞中的直接靶基因，这通过双荧光素酶测定进一步证实。MiR-142- 3 p对肌动蛋白细胞骨架具有强烈的调节作用，如通过在CD 4 + T细胞中的肌动蛋白染色所示。结果表明，miR-142- 3 p在来自阿索患者的CD 4 + T细胞中的表达下调。miR-142- 3 p的下调可以通过其靶基因RAC 1和ROCK 2调节肌动蛋白细胞骨架来增加CD 4 + T细胞向血管壁的迁移。
The migration of CD4+ T cells plays an important role in arteriosclerosis obliterans (ASO). However, the molecular mechanisms involved in CD4+ T cell migration are still unclear. The current study is aimed to determine the expression change of miR-142-3p in CD4+ T cells from patients with ASO and investigate its role in CD4+ T cell migration as well the potential mechanisms involved. We identified by qRT-PCR and in situ hybridization that the expression of miR-142-3p in CD4+ T cells was significantly down-regulated in patients with ASO. Chemokine (C-X-C motif) ligand 12 (CXCL12), a common inflammatory chemokine under the ASO condition, was able to down-regulate the expression of miR-142-3p in cultured CD4+ T cells. Up-regulation of miR-142-3p by lentivirus-mediated gene transfer had a strong inhibitory effect on CD4+ T cell migration both in cultured human cells in vitro and in mouse aortas and spleens in vivo. RAC1 and ROCK2 were identified to be the direct target genes in human CD4+ T cells, which are further confirmed by dual luciferase assay. MiR-142-3p had strong regulatory effects on actin cytoskeleton as shown by the actin staining in CD4+ T cells. The results suggest that the expression of miR-142-3p is down-regulated in CD4+ T cells from patients with ASO. The down-regulation of miR-142-3p could increase the migration of CD4+ T cells to the vascular walls by regulation of actin cytoskeleton via its target genes, RAC1 and ROCK2.
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