Han Xue, Song Yilan, Piao Yihua, Wang Zhiguang, Li Yan, Cui Qingsong, Piao Hongmei, Yan Guanghai
Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, 133002, People's Republic of China.
Department of Respiratory Medicine, Affiliated Hospital of Yanbian University, Yanji, 133000, People's Republic of China.
Cell Mol Life Sci. 2024 Dec 20;82(1):9. doi: 10.1007/s00018-024-05529-0.
Asthma is a chronic inflammatory respiratory disease characterized by recurrent breathing difficulties caused by airway obstruction and hypersensitivity. Although there is diversity in their specific mechanisms, microRNAs (miRNAs) have a significant impact on the development of asthma. Currently, the contribution of miR-130b-3p to asthma remains elusive. The goal of this study was to examine whether miR-130b-3p attenuates house dust mite (HDM)-induced asthma through High-mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/mitochondrial fission protein (DRP1) signaling pathway. We elucidate that miR-130b-3p can bind to the HMGB1 3'UTR, attenuating HMGB1 mRNA and protein levels, and nucleo-cytoplasmic translocation of HMGB1. We observed that miR-130b-3p agomir or HMGB1 CKO attenuated HDM-induced airway inflammation and hyperresponsiveness, and decreased Th2-type cytokines in bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes. Further, HMGB1 CKO contributes to alleviating Th2 inflammation in AT-II cells (CD45.2/CD31/Epcam/proSP-C/MHC-II) from lung single cell suspensions of asthmatic mice by flow cytometry. Our findings identified miR-130b-3p as a potent regulator in asthma that exerts its anti-inflammatory effects by targeting HMGB1 and the subsequent HMGB1/TLR4/DRP1axis, presenting a prospective novel therapeutic avenue for asthma management.
哮喘是一种慢性炎症性呼吸道疾病，其特征是由气道阻塞和超敏反应引起的反复发作的呼吸困难。尽管微小RNA（miRNA）的具体机制存在多样性，但它们对哮喘的发展具有重大影响。目前，miR-130b-3p对哮喘的作用仍不清楚。本研究的目的是探讨miR-130b-3p是否通过高迁移率族蛋白1（HMGB1）/Toll样受体4（TLR4）/线粒体分裂蛋白（DRP1）信号通路减轻屋尘螨（HDM）诱导的哮喘。我们阐明，miR-130b-3p可以与HMGB1的3'非翻译区结合，降低HMGB1的mRNA和蛋白水平，以及HMGB1的核质转运。我们观察到，miR-130b-3p模拟物或HMGB1基因敲除可减轻HDM诱导的气道炎症和高反应性，并降低支气管肺泡灌洗液（BALF）和纵隔淋巴结中Th2型细胞因子的水平。此外，通过流式细胞术，HMGB1基因敲除有助于减轻哮喘小鼠肺单细胞悬液中AT-II细胞（CD45.2/CD31/Epcam/proSP-C/MHC-II）中的Th2炎症。我们的研究结果确定miR-130b-3p是哮喘的一种有效调节因子，它通过靶向HMGB1及随后的HMGB1/TLR4/DRP1轴发挥抗炎作用，为哮喘治疗提供了一条有前景的新途径。
