{"title":"阐明运动对慢性阻塞性肺病及其合并症的有益影响:整合蛋白质组学和免疫学观点。","authors":"Xishuai Wang, Cong Liu, Ruining Liang, Yuehui Zhou, Xiliang Kong, Weichao Wang, Hongwei Wang, Lunan Zhao, Weina Niu, Chao Yi, Fugao Jiang","doi":"10.1111/bph.17328","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and purpose: </strong>Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.</p><p><strong>Experimental approach: </strong>In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.</p><p><strong>Key results: </strong>Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL-33 as a crucial target for the exercise-related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF-κB signalling pathway. Exercise inhibited NF-κB activation by suppressing the CD14/TLR4/MyD88 and TNF-α/TNF-R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B-cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF-α, IFN-γ, and IL-1β, while concurrently increasing insulin expression. The qRT-PCR results were consistent with the proteomic results.</p><p><strong>Conclusion and implications: </strong>In a mouse model, exercise improved COPD and its metabolic comorbidities through immune system regulation and inflammation suppression, offering insights into potential therapeutic targets.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Elucidating the beneficial impact of exercise on chronic obstructive pulmonary disease and its comorbidities: Integrating proteomic and immunological insights.\",\"authors\":\"Xishuai Wang, Cong Liu, Ruining Liang, Yuehui Zhou, Xiliang Kong, Weichao Wang, Hongwei Wang, Lunan Zhao, Weina Niu, Chao Yi, Fugao Jiang\",\"doi\":\"10.1111/bph.17328\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and purpose: </strong>Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.</p><p><strong>Experimental approach: </strong>In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.</p><p><strong>Key results: </strong>Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL-33 as a crucial target for the exercise-related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF-κB signalling pathway. Exercise inhibited NF-κB activation by suppressing the CD14/TLR4/MyD88 and TNF-α/TNF-R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B-cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF-α, IFN-γ, and IL-1β, while concurrently increasing insulin expression. 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引用次数: 0
摘要
背景和目的:体育锻炼是治疗慢性阻塞性肺病(COPD)的有效疗法。然而,体育锻炼对慢性阻塞性肺病有益的机制尚未完全阐明:实验方法:在慢性阻塞性肺病小鼠模型中,通过对生物标记物和肺蛋白质组学的分析,确定了运动改善慢性阻塞性肺病的分子途径:运动改善了慢性阻塞性肺病小鼠的肺功能、肺气肿、小气道疾病、肺部炎症、糖代谢失调和胰岛素抵抗。蛋白质组学分析显示,慢性阻塞性肺病组和慢性阻塞性肺病+运动(COPD + Ex)组之间存在430个差异表达蛋白(DEPs)。GO分析表明,富集的通路主要与免疫反应、炎症过程、胰岛素分泌和葡萄糖代谢过程有关。GO分析显示,IL-33是运动相关改善慢性阻塞性肺病的关键靶点。KEGG分析显示,DEPs在原发性免疫缺陷、产生IgA的肠道免疫网络和NF-κB信号通路中明显富集。运动通过抑制慢性阻塞性肺病小鼠的CD14/TLR4/MyD88和TNF-α/TNF-R1/TRAF2/5通路,抑制了NF-κB的激活。通过抑制 B 细胞受体信号传导,运动抑制了 BCR、IgM、IgD、IgG、IgE 和 IgA 的表达。运动通过抑制促炎介质,包括MHC I、MHC II、TNF-α、IFN-γ和IL-1β,减轻了葡萄糖代谢紊乱和胰岛素抵抗,同时增加了胰岛素的表达。qRT-PCR结果与蛋白质组结果一致:在小鼠模型中,运动通过调节免疫系统和抑制炎症改善了慢性阻塞性肺病及其代谢合并症,为潜在的治疗靶点提供了启示。
Elucidating the beneficial impact of exercise on chronic obstructive pulmonary disease and its comorbidities: Integrating proteomic and immunological insights.
Background and purpose: Physical activity is an effective therapeutic protocol for treating chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the benefits of physical activity in COPD are not fully elucidated.
Experimental approach: In a mouse model of COPD, analysis of biological markers and lung proteomics identified the molecular pathways through which exercise ameliorates COPD.
Key results: Exercise improved pulmonary function, emphysema, small airway disease, pulmonary inflammation, glucose metabolic dysregulation, and insulin resistance in COPD mice. Proteomic analysis revealed 430 differentially expressed proteins (DEPs) between the COPD and COPD + Exercise (COPD + Ex) groups. GO analysis indicated that the enriched pathways were predominantly related to the immune response, inflammatory processes, insulin secretion, and glucose metabolic processes. GO analysis revealed IL-33 as a crucial target for the exercise-related amelioration of COPD. KEGG analysis showed that DEPs were significantly enriched in primary immunodeficiency, the intestinal immune network for IgA production, and the NF-κB signalling pathway. Exercise inhibited NF-κB activation by suppressing the CD14/TLR4/MyD88 and TNF-α/TNF-R1/TRAF2/5 pathways in COPD mice. Exercise inhibited expression of BCR, IgM, IgD, IgG, IgE, and IgA by suppressing B-cell receptor signalling. Exercise attenuated glucose metabolic dysregulation and insulin resistance through the suppression of proinflammatory mediators, including MHC I, MHC II, TNF-α, IFN-γ, and IL-1β, while concurrently increasing insulin expression. The qRT-PCR results were consistent with the proteomic results.
Conclusion and implications: In a mouse model, exercise improved COPD and its metabolic comorbidities through immune system regulation and inflammation suppression, offering insights into potential therapeutic targets.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.