The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases

作者：Xiangguang Shi, Yahui Chen, Mengkun Shi, Fei Gao, Li‐Hao Huang, Wei Wang, Dong Wei, Chenyi Shi, Yuexin Yu, Xueyi Xia, Nana Song, Xiaofeng Chen, Jörg H. W. Distler, Chenqi Lu, Jingyu Chen, Jiucun Wang · 发表于：Lipids in Health and Disease · 年份：2024 · DOI：10.1186/s12944-024-02062-8 · 被引用次数：40 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Extracellular vesicles in disease、Medical Imaging and Pathology Studies

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 phosphatidyletha...