Pan Jing, Yang Qianyuan, Zhou Yao, Deng Huan, Zhu Yifan, Zhao Deyu, Liu Feng
Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China.
Department of Emergency/Critical Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China.
Front Cell Dev Biol. 2020 Jun 30;8:495. doi: 10.3389/fcell.2020.00495. eCollection 2020.
Airway remodeling is one of the most important pathological features of chronic asthma. This study aimed to determine whether microRNA-221 (hereafter, miR-221) can affect airway remodeling in a mouse model of ovalbumin (OVA)-induced chronic asthma.
Adeno-associated viruses (AAVs) "Bearing miR-221 sponges" were used to downregulate miR-221 in asthmatic mice. Staining with hematoxylin and eosin (H&E), Masson trichrome, and periodic acid-Schiff reagent was used to assess histological changes. The affected signaling pathway in mouse airway smooth muscle cells (ASMCs) was also identified by gene chip technology. A PI3K/AKT-inhibitor (LY294002) was used to confirm the role of the pathway in ASMCs.
The inhibition of miR-221 in a murine asthma model was found to reduce airway hyper-responsiveness, mucus metaplasia, airway inflammation, and airway remodeling ( < 0.05). Furthermore, miR-221 was found to regulate collagen deposition in the extracellular matrix (ECM) of ASMCs. Bioinformatics analysis and western blot analysis confirmed that the PI3K-AKT pathway was involved in ECM deposition in ASMCs.
miR-221 might play a crucial role in the mechanism of remodeling via the PI3K/AKT pathway in chronic asthma and it could be considered as a potential target for developing therapeutic strategies.
气道重塑是慢性哮喘最重要的病理特征之一。本研究旨在确定微小RNA-221（以下简称miR-221）是否能在卵清蛋白（OVA）诱导的慢性哮喘小鼠模型中影响气道重塑。
使用携带miR-221海绵的腺相关病毒（AAV）下调哮喘小鼠体内的miR-221。采用苏木精-伊红（H&E）染色、Masson三色染色和过碘酸-希夫试剂染色来评估组织学变化。还通过基因芯片技术鉴定了小鼠气道平滑肌细胞（ASMC）中受影响的信号通路。使用PI3K/AKT抑制剂（LY294002）来确认该通路在ASMC中的作用。
发现在小鼠哮喘模型中抑制miR-221可降低气道高反应性、黏液化生、气道炎症和气道重塑（<0.05）。此外，发现miR-221可调节ASMC细胞外基质（ECM）中的胶原蛋白沉积。生物信息学分析和蛋白质印迹分析证实PI3K-AKT通路参与了ASMC中的ECM沉积。
miR-221可能在慢性哮喘中通过PI3K/AKT通路的重塑机制中起关键作用，并且可被视为开发治疗策略的潜在靶点。
