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

Junyin Gao; Hongjun Liu; Xiaolin Wang; Liping Wang; Jianjun Gu; Yuxiu Wang; Zhiguang Yang; Yunpeng Liu; Jingjing Yang; Zhibin Cai; Yusheng Shu; Lingfeng Min

doi:10.3389/fmed.2022.1030644

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

Front Med (Lausanne). 2023 Jan 12:9:1030644. doi: 10.3389/fmed.2022.1030644. eCollection 2022.

Authors

Junyin Gao¹, Hongjun Liu¹, Xiaolin Wang², Liping Wang³, Jianjun Gu⁴, Yuxiu Wang¹, Zhiguang Yang⁵, Yunpeng Liu⁵, Jingjing Yang¹, Zhibin Cai¹, Yusheng Shu², Lingfeng Min¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, China.
² Department of Thoracic Surgery, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, China.
³ Clinical Medical College, Yangzhou University, Yangzhou, China.
⁴ Department of Cardiology, Institute of Translational Medicine, Clinical Medical College, Yangzhou University, Yangzhou, China.
⁵ Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China.

Abstract

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), immunofluorescence (IF), and immunoprecipitation (IP). The results showed that the differential acetylation modifications of mouse lung tissue are widely involved in cigarette smoke-induced COPD. ALDOA is significantly downregulated and hyperacetylated in the lung tissues of humans and mice with COPD, which might be a potential biomarker for the diagnosis and/or treatment of COPD.

Keywords: COPD; acetylomics; multi-omics associative analysis; proteomics; single-cell RNA sequencing; transcriptomics.

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 81870033) and the Technology Development Planning Projects of Jilin, China (No. 20200201372JC).