Effect and mechanism of microRNA-155 in chronic obstructive pulmonary disease by targeting PIK3R1
- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 5
- DOI:
- 10.13294/j.aps.2022.0072
- Key Word:
- 慢性阻塞性肺疾病;miR-155;PIK3R1;气道平滑肌细胞;增殖;迁移
Abstract： 本研究旨在探讨microRNA-155(miR-155)靶向磷脂酰肌醇-3激酶调节亚基 1(phosphoinositide-3-kinase regulatory subunit 1,PIK3R1)基因调控PTEN/PI3K/Akt信号通路对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)小鼠及香烟提取物(cigarette smoke extract,CSE)刺激的气道平滑肌细胞(airway smooth muscle cells,ASMCs)的影响.采用脂多糖(lipopoly-saccharide,LPS)联合被动吸烟构建小鼠 COPD 模型,建模后采用miR-155 mimics和miR-155 inhibitor进行干预治疗.运用EMKA检测仪检测小鼠肺功能;苏木精-伊红(HE)染色观察肺组织病理变化;酶联免疫吸附法检测支气管肺泡灌洗液(bronchial alveolar lavage fluid,BALF)中TNF-α、IL-6、IL-1β水平.组织贴壁法分离和培养原代ASMCs,CSE刺激后,转染miR-155 mimics或pcDNA PIK3R1,CCK-8及EdU染色法检测ASMCs增殖活性;Transwell及细胞划痕实验检测ASMCs迁移水平;双荧光素酶报告基因实验验证miR-155与PIK3R1的靶向关系;实时荧光定量PCR(qRT-PCR)检测各组小鼠肺组织miRNA-155、PIK3R1 mRNA表达水平;免疫印迹法检测肺组织及ASMCs中Ki67、PNCA、PTEN、p-PI3K、PI3K,p85α、p-Akt、Akt蛋白表达水平.结果显示,miR-155 mimics组小鼠肺功能显著降低,且肺组织PIK3R1表达水平显著增加,而miR-155 inhibitor组上述指标则显著改善;HE染色结果显示miR-155 mimics组较模型组炎性细胞浸润更为明显;miR-155 inhibitor组肺组织病理损伤显著降低,Ki67、PNCA、PI3K及p-Akt蛋白表达显著降低,而PTEN及p85α的蛋白表达显著升高;BALF中TNF-α、IL-6、IL-1β含量显著降低.双荧光素酶报告基因实验分析结果显示,miR-155能够靶向结合PIK3R1;与CSE+miR-155 NC组相比,CSE+miR-155组CSE介导的ASMCs增殖及迁移显著增加,而CSE+miR-155+pcDNA PIK3R1组较miR-155组ASMCs增殖及迁移能力显著减弱,Ki67、PNCA及p-Akt蛋白表达显著降低,而PTEN及p85α的蛋白表达显著升高.以上结果提示,miR-155通过靶向PIK3R1激活PTEN/PI3K/Akt信号通路促进COPD发生和发展,这些发现为miR-155用于治疗COPD提供了新的科学依据和方向.
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