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

Yuexin Yu, Yahui Chen, Dong Wei, Jiucun Wang, Jörg H W Distler, Xiaofeng Chen, Fei Gao, Jingyu Chen, Wei Wang, Xiangguang Shi, Mengkun Shi, Lihao Huang, Chenyi Shi, Xueyi Xia, Nana Song, Chenqi Lu

Journal: Lipids in health and disease 2024;23(1):98

PMID: 38570797

Free Full Text on BioMed Central View on PubMed

Abstract

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.

Address: 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.; Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China.; Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.; Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.; Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.; MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.; MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.; Department of Nephrology, Zhongshan Hospital, Fudan University, Fudan Zhangjiang Institute, Shanghai, People's Republic of China.; Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen, Nuremberg, Germany.; MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China. [email protected].; Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China. [email protected].; Center for Lung Transplantation, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].; Department of Dermatology, Huashan Hospital, and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. [email protected].; Human Phenome Institute, and Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China Fudan University, Shanghai, China. [email protected].; Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Beijing, China. [email protected].; Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China. [email protected].

DOI: 10.1186/s12944-024-02062-8

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/pulmonaryfibrosis.html

MeSH Terms: Humans, Pulmonary Fibrosis, Single-Cell Gene Expression Analysis, Lipid Metabolism, Endothelial Cells, Phospholipids, Cholesterol, Phosphatidylcholines