Zhang Jun, Xu Xiaoyan, Liang Ying, Wu Xiaomin, Qian Zhongqing, Zhang Liming, Wang Ting
Department of Medicine, University of Arizona Tucson, AZ, USA.
Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University Beijing, China.
Am J Transl Res. 2023 Aug 15;15(8):5159-5167. eCollection 2023.
Epidemiologic studies have linked exposure to airborne pollutant particulate matter (PM) with increased rates of chronic cardiopulmonary diseases, including asthma and idiopathic pulmonary fibrosis (IPF). Several investigations have suggested that the epithelial-to-mesenchymal transition (EMT) may contribute to the complex pathobiology of environmental exposure-mediated pulmonary fibrosis. The present study was designed to characterize the mechanisms of PM-mediated EMT in human lung epithelial cells (HBECs).
PM induced significant dose (0-100 μg/ml) and time (0-72 h)-dependent increases in transforming growth factor β (TGFβ) and fibronectin (FN) protein levels in HBECs lysates. PM-activated TGFβ and FN protein production in HBECs was prevented by the antioxidant N-acetyl-cysteine (NAC, 5 mM). Furthermore, the NF-κB inhibitor BAY11-7082 (5 μM) abolished PM-induced FN production in HBECs. Biomarkers of EMT (ACTA2, SNAIL1 and SNAIL2) in PM-treated HBECs were significantly increased at the mRNA level compared to control cells.
These results demonstrate that PM increases protein levels of TGFβ and FN via reactive oxygen species (ROS)-dependent pathways. In addition, PM exposure induces EMT in human lung epithelial cells, supporting a novel mechanism for PM-induced pulmonary fibrosis.
流行病学研究表明，暴露于空气中的污染物颗粒物（PM）与慢性心肺疾病（包括哮喘和特发性肺纤维化（IPF））发病率的增加有关。多项研究表明，上皮-间质转化（EMT）可能参与环境暴露介导的肺纤维化的复杂病理生物学过程。本研究旨在阐明PM介导人肺上皮细胞（HBECs）发生EMT的机制。
PM可显著剂量（0 - 100μg/ml）和时间（0 - 72小时）依赖性地增加HBECs裂解物中转化生长因子β（TGFβ）和纤连蛋白（FN）的蛋白水平。抗氧化剂N - 乙酰半胱氨酸（NAC，5mM）可抑制PM激活的HBECs中TGFβ和FN蛋白的产生。此外，NF - κB抑制剂BAY11 - 7082（5μM）可消除PM诱导的HBECs中FN的产生。与对照细胞相比，PM处理的HBECs中EMT的生物标志物（ACTA2、SNAIL1和SNAIL2）在mRNA水平显著增加。
这些结果表明，PM通过活性氧（ROS）依赖性途径增加TGFβ和FN的蛋白水平。此外，PM暴露可诱导人肺上皮细胞发生EMT，这为PM诱导的肺纤维化提供了一种新机制。
