The role of miR-21 in nickel nanoparticle-induced MMP-2 and MMP-9 production in mouse primary monocytes: In vitro and in vivo studies.

The role of miR-21 in nickel nanoparticle-induced MMP-2 and MMP-9 production in mouse primary monocytes: In vitro and in vivo studies.
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DOI:
10.1016/j.envpol.2020.115597
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发表时间:
2020-12
期刊:
Environmental pollution (Barking, Essex : 1987)
影响因子:
--
通讯作者:
Zhang Q
Zhang Q
中科院分区:
其他
文献类型:
--
作者:
Mo Y;Zhang Y;Mo L;Wan R;Jiang M;Zhang Q

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暴露于金属纳米颗粒会引起肺部和全身的影响。纳米颗粒可以进入血液循环,直接或间接作用于血细胞,如单核细胞。单核细胞/巨噬细胞是最早到达炎症部位的细胞之一,在免疫反应中起着关键作用。本文研究了纳米镍(Nano-Ni)、部分[O]钝化纳米镍(Nano-Ni- p)和碳包覆纳米镍(Nano-Ni- c)对小鼠原代单核细胞MMP-2和MMP-9生成的影响,并探讨了其潜在机制。剂量和时间反应研究表明,野生型(WT)小鼠原代单核细胞暴露于30 μg/mL纳米镍24 h后,MMP-2和MMP-9的产生显著;因此,选择这些剂量和时间点进行以下体外研究。纳米ni和纳米ni - p导致WT小鼠单核细胞miR-21上调,MMP-2、MMP-9、TIMP-1和TIMP-2上调,而miR-21敲除(KO)小鼠不上调,表明miR-21在纳米ni诱导的MMPs和TIMPs上调中起重要作用。然而,纳米ni - c并没有引起这些影响,这表明纳米ni的表面修饰,如碳涂层,减轻了纳米ni诱导的miR-21和MMPs的上调。通过对WT和miR-21 KO小鼠气管内灌注纳米镍颗粒的体内研究进一步证实了这些结果。最后,我们的研究结果表明,WT小鼠的原代单核细胞暴露于Nano-Ni和Nano-Ni- p会导致miR-21的直接靶点RECK的下调,这表明miR-21/RECK通路参与了Nano-Ni诱导的MMP-2和MMP-9的产生。
Exposure to metal nanoparticles causes both pulmonary and systemic effects. Nanoparticles can enter the circulation and act directly or indirectly on blood cells, such as monocytes. Monocytes/macrophages are among the first cells to home to inflammatory sites and play a key role in the immune response. Here we investigated the effects of nickel nanoparticles (Nano-Ni), partially [O]-passivated Nano-Ni (Nano-Ni-P), and carbon-coated Nano-Ni (Nano-Ni-C) on MMP-2 and MMP-9 production in mouse primary monocytes both in vitro and in vivo and explored the potential mechanisms involved. The dose- and time-response studies showed that exposure of primary monocytes from wild-type (WT) mice to 30 μg/mL of Nano-Ni for 24 h caused significant MMP-2 and MMP-9 production; therefore, these dose and time point were chosen for the following in vitro studies. Nano-Ni and Nano-Ni-P caused miR-21 upregulation, as well as MMP-2, MMP-9, TIMP-1 and TIMP-2 upregulation in monocytes from WT, but not miR-21 knock-out (KO), mice, indicating the important role of miR-21 in Nano-Ni-induced MMPs and TIMPs upregulation. However, Nano-Ni-C did not cause these effects, suggesting surface modification of Nano-Ni, such as carbon coating, alleviates Nano-Ni-induced miR-21 and MMPs upregulation. These results were further confirmed by in vivo studies by intratracheal instillation of nickel nanoparticles into WT and miR-21 KO mice. Finally, our results demonstrated that exposure of primary monocytes from WT mice to Nano-Ni and Nano-Ni-P caused downregulation of RECK, a direct miR-21 target, suggesting the involvement of miR-21/RECK pathway in Nano-Ni-induced MMP-2 and MMP-9 production.
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发表时间: 2018-05-11
期刊: Reproductive biology and endocrinology : RB&E
影响因子: --
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影响因子: 3.8
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DOI: 10.3390/molecules16108894
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期刊: Molecules (Basel, Switzerland)
影响因子: --
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