Wang JinHai, Luo Qing, Gu TiJun, An FenQin, Zhou YunZheng, Min YePing, Zhang RuiRen, Jiang YiMing
Department of Emergency, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.
Department of Internal Medicine, People's Hospital of Hainan Tibetan Autonomous Prefecture, Qinghai, Hainan Tibetan Autonomous Prefecture, China.
Immunol Invest. 2025 Feb;54(2):271-295. doi: 10.1080/08820139.2024.2434692. Epub 2024 Nov 26.
To investigate the mechanism of serum exosomes in chronic obstructive pulmonary disease (COPD), especially the effect of lncRNA TBX2-AS1 on macrophage polarization.
Screen differentially expressed genes through bioinformatics analysis, detect the expression of related molecules in clinical samples and cell experiments, construct a mouse model and conduct functional rescue experiments, using various experimental techniques such as RT - qPCR, Western Blot, flow cytometry, ELISA, and luciferase reporter assay.
TBX2-AS1 is highly expressed in the serum and serum exosomes of COPD patients, and it can promote macrophage M1 polarization and inhibit M2 polarization; it exerts its role by negatively regulating the miR-423-5p/miR-23b - 3p axis, where miR-423-5p inhibits CELSR2 expression to prevent M1 polarization, and miR-23b-3p inhibits NEK6 expression to promote M2 polarization; experiments, down-regulation of CELSR2/NEK6 can reverse the promoting effect of COPD serum exosomes on lung injury and inflammation.
COPD serum exosomes deliver TBX2-AS1 to macrophages, regulate the miR-423-5p-CELSR2/miR-23b-3p-NEK6 pathway, affect macrophage polarization, and exacerbate the progression of COPD, providing new directions and potential targets for the diagnosis and treatment of COPD.
探讨血清外泌体在慢性阻塞性肺疾病（COPD）中的作用机制，尤其是长链非编码RNA TBX2-AS1对巨噬细胞极化的影响。
通过生物信息学分析筛选差异表达基因，在临床样本和细胞实验中检测相关分子的表达，构建小鼠模型并进行功能挽救实验，采用RT-qPCR、Western Blot、流式细胞术、ELISA和荧光素酶报告基因检测等多种实验技术。
TBX2-AS1在COPD患者的血清和血清外泌体中高表达，可促进巨噬细胞M1极化并抑制M2极化；它通过负调控miR-423-5p/miR-23b-3p轴发挥作用，其中miR-423-5p抑制CELSR2表达以阻止M1极化，miR-23b-3p抑制NEK6表达以促进M2极化；实验表明，下调CELSR2/NEK6可逆转COPD血清外泌体对肺损伤和炎症的促进作用。
COPD血清外泌体将TBX2-AS1传递给巨噬细胞，调节miR-423-5p-CELSR2/miR-23b-3p-NEK6通路，影响巨噬细胞极化，加剧COPD进展，为COPD的诊断和治疗提供了新方向和潜在靶点。
