外泌体在支气管哮喘发病机制中的作用

The role of exosomes in the pathogenesis of bronchial asthma

哮喘是一种以气道高反应性为特征的慢性气道炎症性疾病。嗜酸性粒细胞、中性粒细胞、肥大细胞能够分泌炎症因子引起炎症反应,介导周围组织破坏,诱导气道黏液高分泌,增加气道高反应性。成纤维细胞在长期慢性气道炎症刺激下导致管腔狭窄、气道高反应性。上皮细胞调节气道平滑肌张力,在损伤和炎症刺激时刺激炎症细胞内流以及分泌大量炎性和营养性介质。骨髓间充质干细胞可以快速分化修复损伤肺部细胞、改善哮喘气道炎症状态。miRNA广泛参与细胞增殖、分化、转运体调控及多种疾病的进展和转移。研究发现,外泌体与哮喘、癌症、心血管疾病等多种炎症疾病的发病机制有关。外泌体是一种广泛分布于唾液、血浆、乳汁、脑脊液、尿液和支气管肺泡灌洗液等体液中的纳米级囊泡,含多种蛋白质、DNA、mRNA、miRNA和脂质,外泌体具有诱导炎症细胞增殖、迁移、分化、凋亡、调节机体免疫应答、运输核酸参与细胞间通讯等作用。不同细胞可分泌包含有特定内含物的外泌体,能够参与细胞间的物质传递和信号转导。近年来人们逐渐认识到不同细胞来源的外泌体及其相关的miRNA在哮喘发病过程中起重要作用。本文就以上不同细胞来源的外泌体、外泌体miRNA在哮喘发病机制方面的研究进行综述,为哮喘的防治提供新靶点。

Asthma is a chronic inflammatory disease characterized by high airway reactivity. Eosinophils, neutrophils and mast cells can secrete inflammatory cytokines to induce inflammatory responses, mediate the destruction of surrounding tissues, and induce high secretion of airway mucus to increase airway hyperresponsiveness. Fibroblasts stimulate chronic airway inflammation for a long time, which leads to narrow lumen and high airway reactivity. The role of epithelial cells in regulating airway smooth muscle tone stimulates the flow of inflammatory cells and secretes a large number of inflammatory and nutrient mediators during injury and inflammatory stimulation. Bone marrow mesenchymal stem cells can rapidly differentiate and repair damaged lung cells and improve airway inflammation in asthma. Micrornas(miRNAs) are widely involved in cell proliferation and differentiation, transporter regulation, and progression and metastasis of a variety of diseases. Exosomes have been found to be associated with the pathogenesis of asthma, cancer, cardiovascular disease and other inflammatory diseases. Exosomes are nano-sized vesicles, widely distributed in the secretion of saliva, blood, breast milk, cerebrospinal fluid, urine and bronchoalveolar lavage fluid, contains many proteins, DNA, mRNA, miRNAs and lipid. Exosomes can inflammation, cell proliferation, migration, differentiation, apoptosis, regulate the body’s immune response, transportation, nucleic acid involved in intercellular communication etc. Different cells can secrete exosomes containing specific inclusions and can participate in intercellular substance transfer and signal transduction. In recent years, it has been gradually recognized that exosomes from different cell sources and their related miRNAs play an important role in the pathogenesis of asthma. In this paper, the studies on the pathogenesis of asthma of exosomes and exosomal miRNAs from different cell sources above were reviewed, providing new targets for the prevention and treatment of asthma.