Mechanism of miR-130b-3p in relieving airway inflammation in asthma through HMGB1-TLR4-DRP1 axis

作者：Xue Han, Yilan Song, Yihua Piao, Zhiguang Wang, Yan Li, Qingsong Cui, Hongmei Piao, Guanghai Yan · 发表于：Cellular and Molecular Life Sciences · 年份：2024 · DOI：10.1007/s00018-024-05529-0 · 被引用次数：7 · 研究领域：Advanced Glycation End Products research、Asthma and respiratory diseases、Inflammation biomarkers and pathways

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.