miR-212/132 attenuates OVA-induced airway inflammation by inhibiting mast cells activation through MRGPRX2 and ASAP1

Abstract

Allergic asthma is a chronic inflammatory disease of airways involving complex mechanisms, including MAS-related GPR family member X2 (MRGPRX2) and its orthologue MRGPRB2 on mast cells (MCs). Although miRNAs have been previously shown to related to allergic asthma, the role of miR-212/132 in this process has not been studied. In this study, the predicted pairing of miRNAs and MRGPRX2 (MRGPRB2) mRNAs was carried out by online databases and the function was verify using in vivo and in vitro experiments. Database prediction showed that miR-212/132 interact with MRGPRX2 and MRGPRB2. miR-212/132 mimics alleviated MRGPRB2 mRNA expression as well as pathology changes in lungs and AHR of mice with airway inflammation in vivo. The expression level of MRGPRB2 in the mice lungs after inhaled OVA was also decreased by miR-212/132 mimics. Meanwhile, miR-212/132 inhibited MCs degranulation and cytokines release triggered by C48/80 in vitro. Further, ASAP1 (ARF GTPase-Activating Protein 1) was selected from the junction related pathways using RNAseq and KEGG enrichment. ASAP1 mRNA level was upregulated in airway inflammation and MCs activation and decreased by miR-212/132 mimics. miR-212/132 attenuated OVA-induced airway inflammation by inhibiting MCs activation through MRGPRX2 and ASAP1.

Keywords: ASAP1; Asthma; MRGPRX2; Pseudo-allergy; miR212/132; microRNA.