Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease

作者：Junyin Gao, Hongjun Liu, Xiaolin Wang, Liping Wang, Jianjun Gu, Yuxiu Wang, Zhiguang Yang, Yunpeng Liu, Jingjing Yang, Zhi-Bin Cai, Yusheng Shu, Lingfeng Min · 发表于：Frontiers in Medicine · 年份：2023 · DOI：10.3389/fmed.2022.1030644 · 被引用次数：11 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、RNA modifications and cancer、Epigenetics and DNA Methylation

We aimed to study the molecular mechanisms of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke more comprehensively and systematically through different perspectives and aspects and to explore the role of protein acetylation modification in COPD. We established the COPD model by exposing C57BL/6J mice to cigarette smoke for 24 weeks, then analyzed the transcriptomics, proteomics, and acetylomics data of mouse lung tissue by RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and associated these omics data through unique algorithms. This study demonstrated that the differentially expressed proteins and acetylation modification in the lung tissue of COPD mice were co-enriched in pathways such as oxidative phosphorylation (OXPHOS) and fatty acid degradation. A total of 19 genes, namely, ENO3, PFKM, ALDOA, ACTN2, FGG, MYH1, MYH3, MYH8, MYL1, MYLPF, TTN, ACTA1, ATP2A1, CKM, CORO1A, EEF1A2, AKR1B8, MB , and STAT1 , were significantly and differentially expressed at all the three levels of transcription, protein, and acetylation modification simultaneously. Then, we assessed the distribution and expression in different cell subpopulations of these 19 genes in the lung tissues of patients with COPD by analyzing data from single-cell RNA sequencing (scRNA-seq). Finally, we carried out the in vivo experimental verification using mouse lung tissue through quantitative real-time PCR (qRT-PCR), Western blotting (WB), immunofluores...