Multi-omics analysis unravels dysregulated lysosomal function and lipid metabolism involved in sub-chronic particulate matter-induced pulmonary injury

Lifeng Yan; Shangheng Chen; Chenchen Hou; Junyi Lin; Weining Xiong; Yiwen Shen; Tianyu Zhou

doi:10.1016/j.scitotenv.2022.155642

Multi-omics analysis unravels dysregulated lysosomal function and lipid metabolism involved in sub-chronic particulate matter-induced pulmonary injury

Sci Total Environ. 2022 Aug 25:836:155642. doi: 10.1016/j.scitotenv.2022.155642. Epub 2022 May 4.

Authors

Lifeng Yan¹, Shangheng Chen², Chenchen Hou¹, Junyi Lin², Weining Xiong³, Yiwen Shen⁴, Tianyu Zhou⁵

Affiliations

¹ Department of Respiratory and Critical Care, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
² Department of Forensic Medicine, Shanghai Medical College of Fudan University, Shanghai 200032, China.
³ Department of Respiratory and Critical Care, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
⁴ Department of Forensic Medicine, Shanghai Medical College of Fudan University, Shanghai 200032, China. Electronic address: shenyiwen@fudan.edu.cn.
⁵ Department of Respiratory and Critical Care, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: zty2712@hotmail.com.

PMID: 35525343
DOI: 10.1016/j.scitotenv.2022.155642

Abstract

Particulate matter (PM) is a huge environmental threat and is of major public concern. Oxidative stress and systemic inflammation are known factors that contribute to PM- related damage; however, a systematic understanding of the deleterious pulmonary effects of PM using multi-omics analysis is lacking. In this study, we performed transcriptomic, proteomic, and metabolomic analyses in a mouse model exposed to PM for three months to identify molecular changes in lung tissues. We identified 1690 genes, 326 proteins, and 67 metabolites exhibiting significant differences between PM-challenged and control mice (p < 0.05). Differentially expressed genes and proteins regulated in PM-challenged mice were involved in lipid metabolism and in the immune and inflammatory response processes. Moreover, a comprehensive analysis of transcript, protein, and metabolite datasets revealed that the genes, proteins, and metabolites in the PM-treated group were involved in lysosomal function and lipid metabolism. Specifically, Cathepsin D (Ctsd), Ferritin light chain (Ftl), Lactotransferrin (Ltf), Lipocalin 2 (Lcn2), and Prosaposin (Psap) were major proteins/genes associated with PM-induced pulmonary damage, while two lipid molecules PC (18:1(11Z)/16:0) and PA (16:0/18:1(11Z)) were major metabolites related to PM-induced pulmonary injury. In summary, lipid metabolism might be used as successful precautions and therapeutic targets in PM-induced pulmonary injury to maintain the stability of cellular lysosomal function.

Keywords: Lipid metabolism; Lysosomal function; Multi-omics; Particulate matter; Pulmonary injury.

MeSH terms

Animals
Lipid Metabolism
Lung Injury* / chemically induced
Lysosomes
Mice
Particulate Matter* / toxicity
Proteomics

Substances

Particulate Matter