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参与全身炎症和谷胱甘肽代谢的基因表达模式揭示慢性阻塞性肺疾病的恶化

Pattern of Expression of Genes Involved in Systemic Inflammation and Glutathione Metabolism Reveals Exacerbation of COPD.

作者信息

Oit-Wiscombe Ingrid, Virág László, Kilk Kalle, Soomets Ursel, Altraja Alan

机构信息

Department of Pulmonology, University of Tartu, 50406 Tartu, Estonia.

Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.

出版信息

Antioxidants (Basel). 2024 Aug 6;13(8):953. doi: 10.3390/antiox13080953.

Abstract

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD. The expression of modulatory subunit of glutamyl-cysteine ligase was higher and that of its catalytic subunit, together with the expression of dipeptidyl peptidase 4, was lower in COPD patients compared with non-obstructive smokers and non-smokers. Leukotriene A4 hydrolase saw increased expression in patients with COPD according to disease severity compared to non-obstructive individuals, whereas the expression of GSH peroxidase increased in non-obstructive smokers and COPD patients with the growing number of pack-years smoked. The results corroborate COPD and its acute exacerbation as a complex systemic disorder demonstrating distinct associations with the expression of enzymes linked to inflammation and the regulation of GSH metabolism.

摘要

为了验证它们作为慢性阻塞性肺疾病(COPD)全身生物标志物的假设,我们分析了外周血单核细胞(PBMC)中与全身炎症和谷胱甘肽(GSH)代谢相关的酶的mRNA表达。这些细胞取自表现为慢性阻塞性肺疾病急性加重(AE-COPD)的患者、稳定期COPD患者,以及非阻塞性吸烟者和非吸烟者。与AE-COPD相关的是,聚(ADP-核糖)聚合酶-1的表达增加,而组蛋白脱乙酰基酶2的表达降低。与非阻塞性吸烟者和非吸烟者相比,COPD患者中谷氨酰半胱氨酸连接酶调节亚基的表达较高,而其催化亚基的表达以及二肽基肽酶4的表达较低。与非阻塞性个体相比,根据疾病严重程度,COPD患者中白三烯A4水解酶的表达增加,而随着吸烟包年数的增加,非阻塞性吸烟者和COPD患者中谷胱甘肽过氧化物酶的表达增加。结果证实COPD及其急性加重是一种复杂的全身疾病,与炎症相关酶的表达和GSH代谢调节存在明显关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/11351727/648bced7cfee/antioxidants-13-00953-g001.jpg

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