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

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 b...

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Autores principales: Gao, Junyin, Liu, Hongjun, Wang, Xiaolin, Wang, Liping, Gu, Jianjun, Wang, Yuxiu, Yang, Zhiguang, Liu, Yunpeng, Yang, Jingjing, Cai, Zhibin, Shu, Yusheng, Min, Lingfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877466/
https://www.ncbi.nlm.nih.gov/pubmed/36714109
http://dx.doi.org/10.3389/fmed.2022.1030644
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author Gao, Junyin
Liu, Hongjun
Wang, Xiaolin
Wang, Liping
Gu, Jianjun
Wang, Yuxiu
Yang, Zhiguang
Liu, Yunpeng
Yang, Jingjing
Cai, Zhibin
Shu, Yusheng
Min, Lingfeng
author_facet Gao, Junyin
Liu, Hongjun
Wang, Xiaolin
Wang, Liping
Gu, Jianjun
Wang, Yuxiu
Yang, Zhiguang
Liu, Yunpeng
Yang, Jingjing
Cai, Zhibin
Shu, Yusheng
Min, Lingfeng
author_sort Gao, Junyin
collection PubMed
description 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.
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spelling pubmed-98774662023-01-27 Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease Gao, Junyin Liu, Hongjun Wang, Xiaolin Wang, Liping Gu, Jianjun Wang, Yuxiu Yang, Zhiguang Liu, Yunpeng Yang, Jingjing Cai, Zhibin Shu, Yusheng Min, Lingfeng Front Med (Lausanne) Medicine 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. Frontiers Media S.A. 2023-01-12 /pmc/articles/PMC9877466/ /pubmed/36714109 http://dx.doi.org/10.3389/fmed.2022.1030644 Text en Copyright © 2023 Gao, Liu, Wang, Wang, Gu, Wang, Yang, Liu, Yang, Cai, Shu and Min. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Gao, Junyin
Liu, Hongjun
Wang, Xiaolin
Wang, Liping
Gu, Jianjun
Wang, Yuxiu
Yang, Zhiguang
Liu, Yunpeng
Yang, Jingjing
Cai, Zhibin
Shu, Yusheng
Min, Lingfeng
Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
title Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
title_full Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
title_fullStr Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
title_full_unstemmed Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
title_short Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
title_sort associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877466/
https://www.ncbi.nlm.nih.gov/pubmed/36714109
http://dx.doi.org/10.3389/fmed.2022.1030644
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