MiR-24 regulates obstructive pulmonary disease in rats via S100A8.

IF 1.5 4区医学 Q3 RESPIRATORY SYSTEM Experimental Lung Research Pub Date : 2024-01-01 Epub Date: 2024-10-11 DOI:10.1080/01902148.2024.2411852

Sha Guo, Qin Liu, Tingting Tan, Xiaoju Chen

{"title":"MiR-24 regulates obstructive pulmonary disease in rats via S100A8.","authors":"Sha Guo, Qin Liu, Tingting Tan, Xiaoju Chen","doi":"10.1080/01902148.2024.2411852","DOIUrl":null,"url":null,"abstract":"Purpose: Chronic obstructive pulmonary disease (COPD) is a persistent inflammatory disorder characterized by minor airway inflammation and emphysema involving various cell types and cytokines. MicroRNAs (miRNAs) have emerged as critical regulators in the pathogenesis of lung diseases. This study investigates the impact of microRNA-24 (miR-24) on airway inflammatory responses in a rat model of COPD.Materials and methods: The model was established by combining cigarette smoke exposure and lipopolysaccharide stimulation, and rat lung tissues were transfected with adeno-associated viruses overexpressing miR-24. Pathological changes in the lung were assessed using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, and interleukin-8, were measured using enzyme-linked immunosorbent assay. Expression of miR-24 and S100A8 was detected through quantitative reverse transcription PCR, while protein levels of S100A8, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were assessed using western blotting. Bioinformatics analysis and dual-luciferase reporter assay were performed to determine the relationship between S100A8 and miR-24.Results: The results demonstrated the downregulation of miR-24 in rats with COPD, and its overexpression resulted in a significant decrease in S1008 mRNA levels. Additionally, the protein level of S100A8 was significantly increased in the lung tissues of COPD rats. The upregulation of miR-24, however, not only inhibited the protein expression of S100A8, TLR4, and MyD88 in lung tissues but also reduced the release of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid, thereby attenuating inflammatory responses and pathological injuries in the lung.Conclusions: Our data suggest that miR-24 attenuates airway inflammatory responses in COPD by inhibiting the TLR4/MyD88 pathway via targeting S100A8.","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"50 1","pages":"172-183"},"PeriodicalIF":1.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Lung Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01902148.2024.2411852","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: Chronic obstructive pulmonary disease (COPD) is a persistent inflammatory disorder characterized by minor airway inflammation and emphysema involving various cell types and cytokines. MicroRNAs (miRNAs) have emerged as critical regulators in the pathogenesis of lung diseases. This study investigates the impact of microRNA-24 (miR-24) on airway inflammatory responses in a rat model of COPD.

Materials and methods: The model was established by combining cigarette smoke exposure and lipopolysaccharide stimulation, and rat lung tissues were transfected with adeno-associated viruses overexpressing miR-24. Pathological changes in the lung were assessed using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, and interleukin-8, were measured using enzyme-linked immunosorbent assay. Expression of miR-24 and S100A8 was detected through quantitative reverse transcription PCR, while protein levels of S100A8, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were assessed using western blotting. Bioinformatics analysis and dual-luciferase reporter assay were performed to determine the relationship between S100A8 and miR-24.

Results: The results demonstrated the downregulation of miR-24 in rats with COPD, and its overexpression resulted in a significant decrease in S1008 mRNA levels. Additionally, the protein level of S100A8 was significantly increased in the lung tissues of COPD rats. The upregulation of miR-24, however, not only inhibited the protein expression of S100A8, TLR4, and MyD88 in lung tissues but also reduced the release of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid, thereby attenuating inflammatory responses and pathological injuries in the lung.

Conclusions: Our data suggest that miR-24 attenuates airway inflammatory responses in COPD by inhibiting the TLR4/MyD88 pathway via targeting S100A8.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

MiR-24 通过 S100A8 调节大鼠的阻塞性肺病

目的：慢性阻塞性肺疾病（COPD）是一种持续性炎症性疾病，其特征是轻微的气道炎症和肺气肿，涉及各种细胞类型和细胞因子。微小 RNA（miRNA）已成为肺部疾病发病机制中的关键调控因子。本研究探讨了微RNA-24（miR-24）对慢性阻塞性肺病大鼠模型气道炎症反应的影响：大鼠肺组织转染了过表达 miR-24 的腺相关病毒。用苏木精和伊红染色法评估肺部的病理变化。用酶联免疫吸附法测定了促炎细胞因子（包括肿瘤坏死因子-α、白细胞介素-6和白细胞介素-8）的水平。通过定量反转录 PCR 检测了 miR-24 和 S100A8 的表达，并采用 Western 印迹法评估了 S100A8、Toll 样受体 4（TLR4）和髓样分化初级反应 88（MyD88）的蛋白水平。生物信息学分析和双荧光素酶报告实验确定了 S100A8 与 miR-24 之间的关系：结果：研究结果表明，在慢性阻塞性肺病大鼠体内，miR-24 下调，其过表达导致 S1008 mRNA 水平显著下降。此外，慢性阻塞性肺病大鼠肺组织中 S100A8 蛋白水平明显升高。然而，miR-24 的上调不仅抑制了肺组织中 S100A8、TLR4 和 MyD88 的蛋白表达，还减少了血浆和支气管肺泡灌洗液中促炎细胞因子的释放，从而减轻了肺部的炎症反应和病理损伤：我们的数据表明，miR-24 通过靶向 S100A8 抑制 TLR4/MyD88 通路，从而减轻慢性阻塞性肺病的气道炎症反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Experimental Lung Research 医学-呼吸系统

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Experimental Lung Research publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. Emphasis is placed on investigations concerned with molecular, biochemical, and cellular mechanisms of normal function, pathogenesis, and responses to injury. The journal publishes reports on important methodological advances on new experimental modes. Also published are invited reviews on important and timely research advances, as well as proceedings of specialized symposia. Authors can choose to publish gold open access in this journal.