PDF(Pubmed)
Abstract：
UNASSIGNED: Chronic obstructive pulmonary disease (COPD) is currently listed as the 3rd leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood.
UNASSIGNED: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics.
UNASSIGNED: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells.
UNASSIGNED: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.
UNASSIGNED: In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics.
UNASSIGNED: ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells.
UNASSIGNED: Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.
摘要：
■慢性阻塞性肺疾病（COPD）目前被列为美国第三大死亡原因。累积数据显示COPD发生与患者电子尼古丁递送系统(ENDS)的使用之间的关联。然而,COPD的潜在发病机制尚未完全了解.
■在当前的研究中，对bENaC过表达的小鼠(bENaC小鼠)进行全身ENDS暴露。COPD相关特征包括肺气肿，粘液积聚,通过组织染色检查炎症和纤维化，FACS分析,细胞因子测量。通过包括染色在内的多种检测方法进一步评估肺泡上皮细胞的细胞死亡和铁凋亡。FACS分析和脂质组学。
■暴露于ENDS的小鼠表现出增强的肺气肿和粘液积聚，提示ENDS暴露促进COPD特征。ENDS暴露也增加了支气管肺泡灌洗中的免疫细胞浸润和肺部多种COPD相关细胞因子的水平，包括CCL2、IL-4、IL-13、IL-10、M-CSF、和TNF-α。此外，我们观察到暴露于ENDS的小鼠纤维化增加，如胶原蛋白沉积升高和a-SMA+肌成纤维细胞积累所证明的。通过调查ENDS如何促进COPD的可能机制，我们证明ENDS暴露诱导肺泡上皮细胞的细胞死亡，通过TUNEL染色和膜联蛋白V/PIFACS分析证明。此外，我们发现ENDS暴露导致脂质失调，包括TAG（9种）和磷脂（34种）。由于大多数这些脂质物种与铁死亡高度相关，我们证实ENDS还增强了I型和II型肺泡上皮细胞中的铁凋亡标志物CD71。
■总的来说，我们的数据显示，ENDS暴露会加剧bENaC小鼠的COPD特征，包括肺气肿，粘液积聚,肺部异常炎症，和纤维化，这涉及到COPD发展的影响，通过诱导肺铁死亡。
■在当前的研究中，对bENaC过表达的小鼠(bENaC小鼠)进行全身ENDS暴露。COPD相关特征包括肺气肿，粘液积聚,通过组织染色检查炎症和纤维化，FACS分析,细胞因子测量。通过包括染色在内的多种检测方法进一步评估肺泡上皮细胞的细胞死亡和铁凋亡。FACS分析和脂质组学。
■暴露于ENDS的小鼠表现出增强的肺气肿和粘液积聚，提示ENDS暴露促进COPD特征。ENDS暴露也增加了支气管肺泡灌洗中的免疫细胞浸润和肺部多种COPD相关细胞因子的水平，包括CCL2、IL-4、IL-13、IL-10、M-CSF、和TNF-α。此外，我们观察到暴露于ENDS的小鼠纤维化增加，如胶原蛋白沉积升高和a-SMA+肌成纤维细胞积累所证明的。通过调查ENDS如何促进COPD的可能机制，我们证明ENDS暴露诱导肺泡上皮细胞的细胞死亡，通过TUNEL染色和膜联蛋白V/PIFACS分析证明。此外，我们发现ENDS暴露导致脂质失调，包括TAG（9种）和磷脂（34种）。由于大多数这些脂质物种与铁死亡高度相关，我们证实ENDS还增强了I型和II型肺泡上皮细胞中的铁凋亡标志物CD71。
■总的来说，我们的数据显示，ENDS暴露会加剧bENaC小鼠的COPD特征，包括肺气肿，粘液积聚,肺部异常炎症，和纤维化，这涉及到COPD发展的影响，通过诱导肺铁死亡。
