Department of Dermatology, Huashan Hospital, and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Human Phenome Institute, and Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China Fudan University, Shanghai, China.
Lipids Health Dis. 2024 Apr 3;23(1):98. doi: 10.1186/s12944-024-02062-8.
Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids' biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.
肺纤维化（PF）是一种严重的肺部疾病，可供选择的治疗方法有限。最近的证据越来越多地指出，异常的脂质代谢是 PF 发病机制的一个关键因素。我们的最新研究确定了低密度脂蛋白（LDL）的失调是 PF 的一个新的风险因素，导致肺泡上皮细胞和内皮细胞损伤以及成纤维细胞激活。在这项研究中，我们首先综合总结了关于 PF 中发现的脂质代谢物变化的已发表文献，包括磷脂、糖脂、类固醇、脂肪酸、甘油三酯和脂蛋白。然后，我们重新分析了两个 PF 的单细胞 RNA 测序（scRNA-seq）数据集，发现了负责这些脂质生物合成、分解代谢、运输和修饰过程的脂质代谢基因。有趣的是，我们发现巨噬细胞是脂质代谢最活跃的细胞类型，PF 中的巨噬细胞几乎改变了所有脂质代谢基因。在 2 型肺泡上皮细胞中，脂质代谢差异表达基因（DEGs）主要与胞苷二磷酸二酰基甘油途径、胆固醇代谢和甘油三酯合成有关。内皮细胞部分负责鞘磷脂、磷脂酰胆碱和磷脂酰乙醇胺的重新编程，因为它们的代谢基因在 PF 中失调。成纤维细胞可能导致 PF 中胆固醇、磷脂酰胆碱和磷脂酰乙醇胺代谢异常。因此，PF 中重编程的脂质谱可能归因于不同细胞类型中脂质代谢基因的异常表达。总之，这些见解强调了靶向脂质代谢在开发创新治疗策略中的潜力，可能导致 PF 患者的总体生存期延长。
