Yuan Qi, Jia Xinyu, Wang Min, Chen Zhongqi, Xu Tingting, Zhang Xijie, Liu Yanan, Wang Zhengxia, Yang Chen, Zhang Mingshun, Zhang Wei, Huang Mao, Ji Ningfei
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
NHC Key Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical University, Nanjing, China.
Allergy Asthma Immunol Res. 2024 Jul;16(4):422-433. doi: 10.4168/aair.2024.16.4.422.
Airway remodeling is a key characteristic of allergic asthma. Epithelial-mesenchymal transition (EMT) induced by various factors, particularly transforming growth factor (TGF)-β1, orchestrates airway remodeling. Protein phosphatase 2A (PP2A), an important serine-threonine phosphatase, is involved in TGF-β1 production and EMT. Long noncoding RNAs (lncRNAs) have emerged as novel players in regulating EMT. Here, we aimed to explore the effects and mechanisms of action of lincR-PPP2R5C, a lncRNA that affects PP2A activity, on airway remodeling in a mouse model of chronic allergic asthma. LincR-PPP2R5C knockout (KO) alleviated inflammatory responses in house dust mite (HDM)-induced chronic allergic asthma. Moreover, airway remodeling and EMT were reduced in lung tissues of lincR-PPP2R5C KO mice. HDM extract induced EMT in airway epithelial cells, which was decreased following lincR-PPP2R5C KO. Mechanistically, lincR-PPP2R5C deficiency enhanced PP2A activity, which inhibited TGF-β1 production in epithelial cells. In conclusion, lincR-PPP2R5C deficiency prevented HDM-induced airway remodeling in mice by reversing EMT, which was mediated by the PP2A/TGF-β1 signaling pathway. Thus, lncRNAs, , lincR-PPP2R5C, may be potential targets to prevent airway remodeling in allergic asthma.
气道重塑是过敏性哮喘的一个关键特征。由多种因素，特别是转化生长因子（TGF）-β1诱导的上皮-间质转化（EMT），协调了气道重塑。蛋白磷酸酶2A（PP2A）是一种重要的丝氨酸-苏氨酸磷酸酶，参与TGF-β1的产生和EMT。长链非编码RNA（lncRNA）已成为调节EMT的新参与者。在此，我们旨在探讨影响PP2A活性的lncRNA——lincR-PPP2R5C在慢性过敏性哮喘小鼠模型中对气道重塑的作用及其机制。敲除lincR-PPP2R5C可减轻屋尘螨（HDM）诱导的慢性过敏性哮喘中的炎症反应。此外，lincR-PPP2R5C基因敲除小鼠肺组织中的气道重塑和EMT减少。HDM提取物可诱导气道上皮细胞发生EMT，而敲除lincR-PPP2R5C后这种现象减少。机制上，lincR-PPP2R5C缺陷增强了PP2A活性，从而抑制上皮细胞中TGF-β1的产生。总之，lincR-PPP2R5C缺陷通过逆转由PP2A/TGF-β1信号通路介导的EMT，预防了HDM诱导的小鼠气道重塑。因此，lncRNA，即lincR-PPP2R5C，可能是预防过敏性哮喘气道重塑的潜在靶点。
