LncRNA H19 via miR-29a-3p is involved in lung inflammation and pulmonary fibrosis induced by neodymium oxide.
LncRNA H19 via miR-29a-3p is involved in lung inflammation and pulmonary fibrosis induced by neodymium oxide.
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DOI：
10.1016/j.ecoenv.2022.114173
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发表时间：
2022-10
影响因子：
6.8
通讯作者：
N. Bu;Yanrong Gao;Yuhang Zhao;Haibo Xia;Xuemin Shi;Yang Deng;Shurui Wang;Yibo Li;Jialing Lv;Qizhan Liu;S. Wang
中科院分区：
文献类型：
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作者：
N. Bu;Yanrong Gao;Yuhang Zhao;Haibo Xia;Xuemin Shi;Yang Deng;Shurui Wang;Yibo Li;Jialing Lv;Qizhan Liu;S. Wang
稀土的职业健康安全和环境健康安全已引起人们的高度重视。在中国的作品中，稀土氧化物Nd2O3得到了广泛的提炼和利用。然而，Nd2O_3致肺损伤的机制尚不清楚。在本研究中，我们发现Nd2O_3暴露引起小鼠肺组织炎症反应和纤维化，这与Nd_2O_3诱导高水平的lncRNAH19(H19)、肿瘤坏死因子受体1(TnFRSF1a)、p-p65和p-IKKβ水平以及低水平的miR-29a-3p有关。此外，在小鼠单核巨噬细胞白血病细胞(RAW 264.7)中，Nd2O_3诱导了炎症反应，增加了H19和TNFRSF1a的水平，降低了miR-29a-3p的水平，并激活了核因子(NF)-κB信号通路。此外，我们建立了miR-29a-3p调节TNFRSF1A表达的机制。上调miR-29a-3p和下调H19可阻断Nd2O3诱导的RAW264.7细胞分泌肿瘤坏死因子-α、巨噬细胞炎性蛋白-1α和IL-6，以及上调肿瘤坏死因子受体-1α和IL-6的水平以及激活核因子-κB信号通路。此外，在经Nd2O3处理的RAW26.4细胞中，H19抑制了针对TNFRSF1a的miR-29a-3p的表达，并激活了NF-κB信号通路，促进了肿瘤坏死因子-α、巨噬细胞趋化蛋白-1α和IL-6的表达。此外，对于小鼠来说，miR-29a-3p的上调逆转了Nd2O3诱导的肺组织炎症、肺纤维化和NF-κB信号通路的激活。综上所述，本研究表明H19通过miR-29a-3p参与了Nd2O_3诱导的肺炎症和肺纤维化，这是Nd_2O_3诱导的肺炎症反应和肺纤维化的机制之一。这一信息有助于开发Nd2O_3致肺损伤的生物标记物。
The occupational and environmental health safety of rare earths has attracted considerable attention. In China, the rare earth neodymium oxide (Nd2O3) is extensively refined and utilized. However, the mechanisms of Nd2O3-induced lung injury are elusive. In the present study, we found that exposure of mice to Nd2O3caused an inflammatory reaction and fibrosis in lung tissues, which was in relation to the Nd2O3-induced higher levels of the lncRNA H19 (H19), tumor necrosis factor receptor 1 (TNFRSF1A), p-p65, and p-IKKβ and lower levels of miR-29a-3p. Further, in mouse monocyte macrophage leukemia cells (RAW264.7), Nd2O3induced an inflammatory reaction, increases of H19 and TNFRSF1A levels, decreases of miR-29a-3p levels, and activation of the nuclear factor (NF)-κB signaling pathway. Further, we established that miR-29a-3p regulates TNFRSF1A expression. Up-regulation of miR-29a-3p and down-regulation of H19 blocked the Nd2O3-induced secretion of TNF-α, MIP-1α, and IL-6; the increases of TNFRSF1A levels; and activation of the NF-κB signaling pathway in RAW264.7 cells. Further, in Nd2O3-treated RAW26.4 cells, H19 inhibited the expression of miR-29a-3p, which targets TNFRSF1A, and activated the NF-κB signaling pathway to enhance the expression of TNF-α, MIP-1α, and IL-6. Moreover, for mice, up-regulation of miR-29a-3p reversed lung tissue inflammation, pulmonary fibrosis, and activation of the NF-κB signaling pathway induced by Nd2O3. In sum, the present investigation shows that H19 via miR-29a-3p is involved in lung inflammation and pulmonary fibrosis induced by Nd2O3, which is a mechanism for the Nd2O3-induced lung inflammatory response and pulmonary fibrosis. This information is useful for development of a biomarker of Nd2O3-induced lung injury.