m⁶A reader IGF2BP2 mediates airway remodeling by stabilizing Dixdc1 in asthma pathogenesis

N6-methyladenosine (m⁶A) modification is a crucial post-transcriptional regulatory mechanism for gene expression. In our previous bioinformatic analysis, we found that many m⁶A genes are involved in asthma pathogenesis; however, the precise regulatory mechanism has not been experimentally validated. Using an in-vitro asthma model (platelet-derived growth factor [PDGF]-BB-stimulated rat airway smooth muscle cells [AMSCs]), we validated dysregulated m⁶A-related genes using qRT-PCR. Functional assays (CCK-8 and wound healing assays) revealed that Igf2bp2 knockdown suppressed AMSC proliferation and migration. Integrated analysis of mRNA-sequencing (Igf2bp2-silenced AMSCs) and RIP-seq identified three asthma-associated targets: Dact1, Dixdc1, and Pdk4. Intriguingly, Dixdc1 transcripts harbored multiple m⁶A motifs, consistent with the RIP-seq data. Actinomycin D assays demonstrated the IGF2BP2-mediated post-transcriptional stabilization of Dixdc1 mRNA, a mechanism corroborated by both PDGF-BB-treated AMSCs and ovalbumin-induced asthmatic rats. Clinically, IGF2BP2-DIXDC1 co-expression was evident in the GEO human airway datasets and asthmatic rat tissues. Pharmacologically, resveratrol attenuated asthmatic phenotypes by suppressing this axis. Our findings delineate an m⁶A-dependent pathway, wherein IGF2BP2 stabilized Dixdc1 to drive airway remodeling, positioning resveratrol as a potential therapeutic agent targeting epitranscriptomic dysregulation in asthma.