Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, PR China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, PR China.
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China.
Toxicol Appl Pharmacol. 2019 Aug 15;377:114616. doi: 10.1016/j.taap.2019.114616. Epub 2019 Jun 8.
Air pollution, especially fine particulate matter (PM, particles <2.5 μm in size), induces adverse health effects on the respiratory system. Uncontrolled proliferation of bronchial epithelial cells, resulting from deregulated cell cycle progression, contributes to pulmonary homeostatic imbalance. Although dysregulation of miRNAs is involved in a variety of pathophysiologic processes, the role of miRNAs in lung injury caused by PM is unclear. In the present study, we found that different concentrations of PM caused a biphasic effect on proliferation of human bronchial epithelial (HBE) cells. PM induced an aberrant cell cycle and proliferation of HBE cells, and up-regulated miR-155 levels with a concentration-dependent manner. High miR-155 expression, mediated by NF-κB activation, produced an accelerated G1/S phase and cell proliferation though the STAT3 pathway, which targeted SOCS1. These findings indicate that NF-κB-mediated miR-155 induces an altered cell cycle through epigenetic modulation of the SOCS1/STAT3 signaling pathway and provide a mechanism for the biphasic effect of different concentrations of PM in inducing respiratory injury.
空气污染，特别是细颗粒物（PM，粒径<2.5μm 的颗粒），会对呼吸系统造成不良健康影响。支气管上皮细胞的不受控制的增殖，源于细胞周期进程的失调，导致肺部的动态平衡失衡。尽管 miRNA 的失调参与了多种病理生理过程，但 miRNA 在 PM 引起的肺损伤中的作用尚不清楚。在本研究中，我们发现不同浓度的 PM 对人支气管上皮（HBE）细胞的增殖产生了双相作用。PM 诱导 HBE 细胞的细胞周期异常和增殖，并呈浓度依赖性地上调 miR-155 水平。高 miR-155 表达，通过 NF-κB 激活介导，通过靶向 SOCS1 的 STAT3 通路，产生加速的 G1/S 期和细胞增殖。这些发现表明，NF-κB 介导的 miR-155 通过 SOCS1/STAT3 信号通路的表观遗传调控诱导改变的细胞周期，并为不同浓度的 PM 诱导呼吸损伤的双相作用提供了一种机制。
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