Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Acupuncture & Chronobiology Key Laboratory of Sichuan Province, Chengdu, Sichuan, China.
J Cell Mol Med. 2023 Dec;27(24):4034-4044. doi: 10.1111/jcmm.17985. Epub 2023 Oct 6.
Airway epithelial cell injury plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, a novel form of Cu-induced programmed cell death known as cuproptosis has not yet been thoroughly investigated in the context of COPD. Clinical reports have suggested that high copper exposure may increase the risk of COPD. In this study, we aimed to determine the expression and potential functions of cuproptosis-related genes and genes associated with copper metabolism in COPD. We initially identified 52 copper metabolism-related genes based on a review of the literature. Subsequently, we calculated the expression levels of these genes using data from four GEO datasets. To gain insights into the activated signalling pathways and underlying mechanisms in COPD patients, we conducted Gene Ontology (GO) and KEGG pathway analyses, examined protein-protein interactions, and performed weighted correlation network analysis. Our findings revealed that 18 key copper metabolism-related genes, including 5 cuproptosis-related genes, were significantly enriched in signalling pathways and biological processes associated with the development of COPD. Further analysis of clinical data and animal experiments confirmed the high expression of certain cuproptosis key regulators, such as DLD and CDKN2A, in both healthy smokers and COPD smokers. Additionally, these regulators exhibited abnormal expression in a COPD rat model. Notably, copper content was found to be elevated in the lung tissues of COPD rats, suggesting its potential involvement in cuproptosis. These findings provide an experimental foundation for further research into the role of cuproptosis in COPD. Targeting copper metabolism-related genes may represent an effective approach for the treatment of COPD.
气道上皮细胞损伤在慢性阻塞性肺疾病（COPD）的发病机制中起着关键作用。然而，一种新形式的铜诱导程序性细胞死亡，即铜死亡，在 COPD 中的研究还不够深入。临床报告表明，高铜暴露可能会增加 COPD 的风险。在本研究中，我们旨在确定 COPD 中铜死亡相关基因和铜代谢相关基因的表达及其潜在功能。我们首先根据文献综述确定了 52 个与铜代谢相关的基因。然后，我们使用来自四个 GEO 数据集的数据计算了这些基因的表达水平。为了深入了解 COPD 患者中激活的信号通路和潜在机制，我们进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，检查了蛋白质-蛋白质相互作用，并进行了加权相关网络分析。我们的研究结果表明，18 个关键的铜代谢相关基因，包括 5 个铜死亡相关基因，在与 COPD 发展相关的信号通路和生物学过程中显著富集。对临床数据和动物实验的进一步分析证实，某些铜死亡关键调节剂，如 DLD 和 CDKN2A，在健康吸烟者和 COPD 吸烟者中表达水平较高。此外，这些调节剂在 COPD 大鼠模型中表现出异常表达。值得注意的是，COPD 大鼠的肺组织中发现铜含量升高，表明其可能参与铜死亡。这些发现为进一步研究铜死亡在 COPD 中的作用提供了实验基础。靶向铜代谢相关基因可能是治疗 COPD 的一种有效方法。
