Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Ecotoxicol Environ Saf. 2023 May;256:114839. doi: 10.1016/j.ecoenv.2023.114839. Epub 2023 Mar 28.
Particulate matter (PM) has become the main risk factor for public health, being linked with an increased risk of respiratory diseases. However, the potential mechanisms underlying PM-induced lung injury have not been well elucidated. In this study, we systematically integrated the metabolomics, lipidomics, and transcriptomics data obtained from the human bronchial epithelial cells (HBECs) exposed to PM to reveal metabolic disorders in PM-induced lung injury. We identified 170 differentially expressed metabolites (82 upregulated and 88 downregulated metabolites), 218 differentially expressed lipid metabolites (125 upregulated and 93 downregulated lipid metabolites), and 1417 differentially expressed genes (643 upregulated and 774 downregulated genes). Seven key metabolites (prostaglandin E2, inosinic acid, L-arginine, L-citrulline, L-leucine, adenosine, and adenosine monophosphate), and two main lipid subclasses (triglyceride and phosphatidylcholine) were identified in PM-exposed HBECs. The amino acid metabolism, lipid metabolism, and carbohydrate metabolism were the significantly enriched pathways of identified differentially expressed genes. Then, conjoint analysis of these three omics data and further qRT-PCR validation showed that arachidonic acid metabolism, glycerolipid metabolism, and glutathione metabolism were the key metabolic pathways in PM-exposed HBECs. The knockout of AKR1C3 in arachidonic acid metabolism or GPAT3 in glycerolipid metabolism could significantly inhibit PM-induced inflammatory responses in HBECs. These results revealed the potential metabolic pathways in PM-exposed HBECs and provided a new target to protect from PM-induced airway damage.
颗粒物（PM）已成为主要的公共健康风险因素，与呼吸道疾病风险增加有关。然而，PM 诱导的肺损伤的潜在机制尚未得到很好的阐明。在这项研究中，我们系统地整合了暴露于 PM 的人支气管上皮细胞（HBEC）的代谢组学、脂质组学和转录组学数据，以揭示 PM 诱导的肺损伤中的代谢紊乱。我们鉴定了 170 个差异表达的代谢物（82 个上调和 88 个下调代谢物）、218 个差异表达的脂质代谢物（125 个上调和 93 个下调脂质代谢物）和 1417 个差异表达的基因（643 个上调和 774 个下调基因）。在暴露于 PM 的 HBEC 中鉴定出 7 种关键代谢物（前列腺素 E2、肌苷酸、L-精氨酸、L-瓜氨酸、L-亮氨酸、腺苷和单磷酸腺苷）和 2 种主要脂质亚类（甘油三酯和磷脂酰胆碱）。鉴定的差异表达基因的显著富集途径是氨基酸代谢、脂质代谢和碳水化合物代谢。然后，对这三种组学数据进行联合分析和进一步的 qRT-PCR 验证表明，花生四烯酸代谢、甘油脂代谢和谷胱甘肽代谢是暴露于 PM 的 HBEC 中的关键代谢途径。在花生四烯酸代谢中敲除 AKR1C3 或在甘油脂代谢中敲除 GPAT3 可显著抑制 HBEC 中 PM 诱导的炎症反应。这些结果揭示了暴露于 PM 的 HBEC 中的潜在代谢途径，并为保护气道免受 PM 诱导的损伤提供了新的靶点。
