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高表达和低表达水平与高炎症活动期肺结核患者肺组织中的两个不同基因特征相关。

High and Low Levels of Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity.

机构信息

Central Tuberculosis Research Institute, 107564 Moscow, Russia.

Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.

出版信息

Int J Mol Sci. 2023 Oct 2;24(19):14839. doi: 10.3390/ijms241914839.

Abstract

P-glycoprotein (encoded by the gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of , , , , and , which correlated with high expression. The second signature was characterized by high expression of and and low expression of . These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment.

摘要

P-糖蛋白(由 基因编码)在调节炎症和降低各种疾病的化疗效果方面具有双重作用,但针对肺结核患者的研究较少。在这项研究中,我们的目的是确定一组与肺结核患者肺部慢性肉芽肿炎症活动度不同的高、低 基因表达相关的基因。我们比较了两组样本(结核瘤活动度中等和高)的基因表达,以确定其特征性基因特征。使用定量 PCR 测定了 65 例手术干预后获得的肉芽肿周围区域样本中的基因表达水平。随后,确定了两个与高炎症活性相关的不同基因特征。第一个特征表现为 、 、 、 和 的表达增加,与高 表达相关。第二个特征的特点是 、 和 的高表达以及 的低表达。这些结果深入了解了各种炎症机制以及与肺结核患者肺部 P-糖蛋白基因表达的关联,并将有助于开发针对宿主的治疗方法,以提高抗结核治疗的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c6c/10573207/736557126bd4/ijms-24-14839-g001.jpg

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