Untargeted metabolomics and transcriptomics identified glutathione metabolism disturbance and PCS and TMAO as potential biomarkers for ER stress in lung

• Published in: Scientific reports Vol. 11; no. 1; pp. 14680 - 13
• Main Authors: Wang, Zijing, Ma, Peng, Wang, Yisa, Hou, Biyu, Zhou, Can, Tian, He, Li, Bowen, Shui, Guanghou, Yang, Xiuying, Qiang, Guifen, Yin, Chengqian, Du, Guanhua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/45; Animals; Biomarkers; Biomarkers - analysis; Biomarkers - metabolism; Bronchopulmonary infection; Cell death; Cresols; Cresols - analysis; Cresols - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum Stress - genetics; Endoplasmic Reticulum Stress - physiology; Energy expenditure; Gene Expression Profiling - methods; Glutathione; Glutathione - metabolism; Homeostasis; Humanities and Social Sciences; Lung - chemistry; Lung - metabolism; Lung - pathology; Lung diseases; Lung Injury - diagnosis; Lung Injury - genetics; Lung Injury - metabolism; Lung Injury - pathology; Male; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Methylamines - analysis; Methylamines - metabolism; Mice; Mice, Inbred C57BL; multidisciplinary; Oxidative Stress - genetics; Oxidative Stress - physiology; Protein folding; Science; Science (multidisciplinary); Signal transduction; Stress; Sulfuric Acid Esters - analysis; Sulfuric Acid Esters - metabolism; Transcriptomics; Trimethylamine; Unfolded Protein Response - genetics; Unfolded Protein Response - physiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-92779-8

Endoplasmic reticulum (ER) stress is a cellular state that results from the overload of unfolded/misfolded protein in the ER that, if not resolved properly, can lead to cell death. Both acute lung infections and chronic lung diseases have been found related to ER stress. Yet no study has been presented integrating metabolomic and transcriptomic data from total lung in interpreting the pathogenic state of ER stress. Total mouse lungs were used to perform LC–MS and RNA sequencing in relevance to ER stress. Untargeted metabolomics revealed 16 metabolites of aberrant levels with statistical significance while transcriptomics revealed 1593 genes abnormally expressed. Enrichment results demonstrated the injury ER stress inflicted upon lung through the alteration of multiple critical pathways involving energy expenditure, signal transduction, and redox homeostasis. Ultimately, we have presented p-cresol sulfate (PCS) and trimethylamine N-oxide (TMAO) as two potential ER stress biomarkers. Glutathione metabolism stood out in both omics as a notably altered pathway that believed to take important roles in maintaining the redox homeostasis in the cells critical for the development and relief of ER stress, in consistence with the existing reports.