miR-181a-5p通过调控HMGB1和NF-κB通路在慢性阻塞性肺疾病小鼠中的作用及机制

IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Manyan Zhang, Yu Lu, Lingling Liu, Xiaoyan Zhang, Jiyu Ning
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引用次数: 1

摘要

慢性阻塞性肺疾病(COPD)是一种常见的呼吸道疾病。本研究探讨了miR-181a-5p在COPD小鼠炎症反应中的作用机制。分别用重组腺相关病毒(rAAv)-miR-181a-5p、si-HMGB1(高迁移率组1)和NF-κB途径抑制剂PDTC预处理后,通过香烟烟雾(CS)暴露建立COPD小鼠模型。HE染色观察肺组织病理变化。收集支气管肺泡灌洗液,用伯爵夫人II型自动细胞计数器计数总细胞、中性粒细胞和淋巴细胞。ELISA法检测各组中性粒细胞弹性蛋白酶(NE)和炎性因子(TNF-α、IL-6、IL-8、IFN-γ)的表达。在starBase上预测miR-181a-5p与HMGB1的结合关系,并通过双荧光素酶实验验证。RT-qPCR检测miR-181a-5p的表达,western blot检测HMGB1、IκBα、p-IκBα的表达。miR-181a-5p在肺组织中的表达水平较低。miR-181a-5p过表达可减轻COPD小鼠的炎症反应和肺组织的病理改变,降低肺部炎症评分、总细胞、中性粒细胞和淋巴细胞以及NE和炎症因子的表达。慢性阻塞性肺病小鼠HMGB1表达水平升高。miR-181a-5p靶向HMGB1。si-HMGB1可减轻COPD小鼠的炎症反应。NF-κB在COPD小鼠中被激活,其证据是i -κB α水平降低,p -κB α水平升高。si-HMGB1显著抑制NF-κB通路的激活。简言之,miR-181a-5p通过靶向HMGB1抑制NF-κB通路,从而减轻COPD小鼠的炎症反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role and Mechanism of miR-181a-5p in Mice with Chronic Obstructive Pulmonary Disease by Regulating HMGB1 and the NF-κB Pathway.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. This study explored the mechanism of miR-181a-5p in the inflammatory response in COPD mice. COPD mouse models were established by cigarette smoke (CS) exposure following pretreatment with recombinant adeno-associated virus (rAAv)-miR-181a-5p, si-HMGB1 (high mobility group box 1), and NF-κB pathway inhibitor PDTC, respectively. Pathological changes of lung tissues were determined by HE staining. Bronchoalveolar lavage fluid was collected to count total cells, neutrophils, and lymphocytes using a Countess II automatic cell counter. Expressions of neutrophil elastase (NE) and inflammatory factors (TNF-α, IL-6, IL-8, and IFN-γ) were detected by ELISA. Binding relationship between miR-181a-5p and HMGB1 was predicted on starBase and validated by dual-luciferase assay. miR-181a-5p expression was detected by RT-qPCR, and expressions of HMGB1, IκBα, and p-IκBα were detected by western blot. The expression level of miR-181a-5p was lower in lung tissues. miR-181a-5p overexpression alleviated inflammatory response and pathological changes of lung tissues in COPD mice, with decreased pulmonary inflammation scores, total cells, neutrophils, and lymphocytes and expressions of NE and inflammatory factors. HMGB1 expression level was increased in COPD mice. miR-181a-5p targeted HMGB1. si-HMGB1 relieved inflammatory responses in COPD mice. NF-κB was activated in COPD mice, evidenced by degraded IκBα and increased p-IκBα levels. si-HMGB1 significantly restrained the activation of NF-κB pathway. Briefly, miR-181a-5p targets HMGB1 to inhibit the NF-κB pathway, thus alleviating the inflammatory response in COPD mice.

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来源期刊
Cells Tissues Organs
Cells Tissues Organs 生物-发育生物学
CiteScore
4.90
自引率
3.70%
发文量
45
审稿时长
6-12 weeks
期刊介绍: ''Cells Tissues Organs'' aims at bridging the gap between cell biology and developmental biology and the emerging fields of regenerative medicine (stem cell biology, tissue engineering, artificial organs, in vitro systems and transplantation biology). CTO offers a rapid and fair peer-review and exquisite reproduction quality. Special topic issues, entire issues of the journal devoted to a single research topic within the range of interests of the journal, are published at irregular intervals.
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