Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
Free Radic Biol Med. 2019 May 1;135:235-244. doi: 10.1016/j.freeradbiomed.2019.03.008. Epub 2019 Mar 14.
Traffic emission is responsible for most small-sized particulate matter (PM) air pollution in urban areas. Several recent studies have indicated that traffic-related PM may aggravate kidney disease. Furthermore, exposure to particulate air pollution may be related to the risk of chronic kidney disease (CKD). However, the underlying molecular mechanisms have not been adequately addressed. In the present study, we studied the mechanisms of renal damage that might be associated with exposure to PM. In a real world of whole-body exposure to traffic-related PM model for 3-6 months, PM in urban ambient air can affect kidney function and induce autophagy, endoplasmic reticulum (ER) stress and apoptosis in kidney tissues. Exposure to traffic-related diesel particulate matter (DPM) led to a reduction in cell viability in human kidney tubular epithelial cells HK-2. DPM increased mitochondrial reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Furthermore, DPM induced ER stress and activated the unfolded protein response (UPR) pathway. Eventually, DPM exposure induced caspase pathways and triggered apoptosis. In addition, DPM induced autophagy through the inhibition of the Akt/mTOR pathway. Autophagy inhibition resulted in significantly increased cytotoxicity and apoptosis. These findings suggest that air pollution in urban areas may cause nephrotoxicity and autophagy as a protective role in PM-induced cytotoxicity.
交通排放是城市地区造成大多数小粒径颗粒物（PM）空气污染的主要原因。最近的几项研究表明，与交通相关的 PM 可能会加重肾脏疾病。此外，暴露于颗粒物空气污染可能与慢性肾病（CKD）的风险相关。然而，其潜在的分子机制尚未得到充分解决。在本研究中，我们研究了可能与 PM 暴露相关的肾脏损伤的机制。在为期 3-6 个月的全身暴露于交通相关 PM 模型的真实世界中，城市环境空气中的 PM 可影响肾功能并在肾脏组织中诱导自噬、内质网（ER）应激和细胞凋亡。暴露于交通相关的柴油颗粒物质（DPM）可降低人肾小管上皮细胞 HK-2 的细胞活力。DPM 增加了线粒体活性氧（ROS）并降低了线粒体膜电位。此外，DPM 诱导 ER 应激并激活未折叠蛋白反应（UPR）途径。最终，DPM 暴露诱导了半胱天冬酶途径并引发了细胞凋亡。此外，DPM 通过抑制 Akt/mTOR 途径诱导自噬。自噬抑制导致细胞毒性和细胞凋亡显著增加。这些发现表明，城市地区的空气污染可能导致肾毒性和自噬作为 PM 诱导的细胞毒性的保护作用。
