| Title | ESR2 regulates PINK1-mediated mitophagy via transcriptional repression of microRNA-423 expression to promote asthma development. | ||
| Author | Kong, Xiaomei; Chen, Ru; Zhang, Lina; Wu, Meiqiong; Wu, Juan; Wei, Yangyang; Dai, Wenjuan; Jiang, Yi | ||
| Journal | Pharmacol Res | Publication Year/Month | 2021-Dec |
| PMID | 34700017 | PMCID | -N/A- |
| Affiliation + expend | 1.Department of Respiratory and Critical Care Medicine, the First Hospital of Shanxi Medical, University, Taiyuan 030002, Shanxi, PR China. Electronic address: XiaomeiK7284@163.com. | ||
Asthma represents an inflammatory airway disease related to the induction of airway eosinophilia, mucus overproduction, and bronchial hyperresponsiveness. This study explored the effects of microRNA-423 (miR-423) on mitophagy and inflammation in asthmatic mice challenged with house dust mites (HDMs) and rhinovirus (RV). By searching for differentially expressed miRNAs in the GSE25230 microarray, miR-423 was identified as our target. Moreover, miR-423 was expressed at low levels in the lung tissues from patients with asthma, and agomiR-423 significantly inhibited RV-induced inflammatory injury and activation of inflammasome signaling in mouse lung tissues. Additionally, miR-423 downregulated the expression of IL-1beta/NLRP3/Caspase-1 inflammasome signaling by targeting phosphatase and tensin homolog-induced putative kinase 1 (PINK1). Furthermore, luciferase reporter experiments and ChIP-qPCR assays revealed that estrogen receptor 2 (ESR2) transcriptionally repressed miR-423 expression by coordinating with H3K9me2 modification of the miR-423 promoter histone. Overall, ESR2 synergized with the H3K9me2 modification of the miR-423 promoter histone to transcriptionally repress miR-423 expression and increase PINK1 expression in lung tissues, resulting in asthma exacerbation.