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评价慢性阻塞性肺疾病中选定的 IL6/STAT3 通路分子和 miRNA 表达。

Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease.

机构信息

Department of Biomedicine and Genetics, Chair of Biology and Medical Microbiology, Medical University of Lodz, St. Pomorska 251, 92-213, Lodz, Poland.

Department of Pneumology, Medical University of Lodz, St. Kopcińskiego 22, 90-153, Lodz, Poland.

出版信息

Sci Rep. 2021 Nov 23;11(1):22756. doi: 10.1038/s41598-021-01950-8.

Abstract

COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miRNA-1, miRNA-106b, miRNA-155, in patients with COPD. Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2021 (A-D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. In induced sputum IL6 was significantly down-regulated in COPD group compared with control (p = 0.0008), while IL6ST were up-regulated (p = 0.05). The results were also statistically significant for STAT3 (p = 0.04) and miRNA-155 (p = 0.03) with higher expression in the current smokers compared to ex-smokers. Higher expression levels for IL6ST (p = 0.03) in COPD patients with the exacerbation history compared to COPD patients without the exacerbation history were noted. Compared induced sputum and PB lymphocytes we observed higher expression of IL6 (p = 0.0003), STAT3 (p = 0.000001) miRNA-106b (p = 0.000069 and miRNA-155 (p = 0.000016) in induced sputum with lower expression of PIAS3 (p = 0.006), IL6ST (p = 0.002) and miRNA-1 (p = 0.001). Differences in gene expression levels of the IL-6/IL6ST/STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.

摘要

COPD 被认为是一种全球性的流行疾病,这是由于污染和烟草暴露的增加所致。因此,以现代疗法为基础的分子机制研究是很重要的。本研究的目的是评估 COPD 患者的基因表达水平、IL-6、IL-6ST、PIAS3、STAT3 和 miRNA-1、miRNA-106b、miRNA-155。从根据 GOLD 2021(A-D)分类临床确诊的 40 名患者(n=40)和对照组(n=20)中收集诱导痰和 PBMC。通过 qPCR 分析基因和 miRNA 表达水平。与对照组相比,COPD 组诱导痰中的 IL6 水平显著下调(p=0.0008),而 IL6ST 上调(p=0.05)。STAT3(p=0.04)和 miRNA-155(p=0.03)的结果也具有统计学意义,与从不吸烟者相比,当前吸烟者的表达更高。与没有加重史的 COPD 患者相比,有加重史的 COPD 患者的 IL6ST 表达水平更高(p=0.03)。与 PB 淋巴细胞相比,我们观察到诱导痰中 IL6(p=0.0003)、STAT3(p=0.000001)、miRNA-106b(p=0.000069)和 miRNA-155(p=0.000016)的表达更高,而 PIAS3(p=0.006)、IL6ST(p=0.002)和 miRNA-1(p=0.001)的表达更低。根据 GOLD 对患者进行分类和吸烟状况的不同,IL-6/IL6ST/STAT3 通路和 miRNA 的基因表达水平存在差异,这表明这些基因在 COPD 发病机制中的重要性,并可能表明它们在监测疾病进程方面具有潜在的应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc30/8610981/a2cba65b87bb/41598_2021_1950_Fig1_HTML.jpg

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