ESR2 regulates PINK1-mediated mitophagy via transcriptional repression of microRNA-423 expression to promote asthma development. (December 2021)

• Record Type: Journal Article
• Authors: Kong, Xiaomei; Chen, Ru; Zhang, Lina; Wu, Meiqiong; Wu, Juan; Wei, Yangyang; Dai, Wenjuan; Jiang, Yi
• Is Part Of: Pharmacological research. Volume 174(2021)
• Publication Date: 2021-12
• Subjects: 3'UTR 3'-untranslated region -- BALF broncho alveolar lavage fluid -- ChIP chromatin immunoprecipitation -- ESR2 estrogen receptor 2 -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- HDMs house dust mites -- HE hematoxylin-eosin -- IL interleukin -- miR-423 microRNA-423 -- mt mutant -- NLRP3 NOD-like receptor family pyrin domain containing 3 -- OD optical density -- PBS phosphate buffered saline -- PINK1 phosphatase and tensin homologue-induced putative kinase 1 -- RV rhinovirus -- TNF tumor necrosis factor -- wt wild-type; Asthma -- ESR2 -- MicroRNA-423 -- PINK1 -- IL-1β/NLRP3/Caspase-1 inflammasome signaling -- Mitophagy; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105956
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: 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-1β/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. Graphical Abstract: ga1