Airway Smooth Muscle in Asthma: Insights from a Transcriptomic Meta-analysis

Background Airway smooth muscle (ASM) cells are the central to bronchoconstriction and airway hyperresponsiveness in asthma, yet a comprehensive view of their transcriptional landscape has been lacking. Methods We performed a meta-analysis of publicly available transcriptomic datasets comparing ASM cells isolated from individuals with asthma and healthy controls. We included studies that met predefined inclusion criteria, comprising primary human ASM cells isolated from 26 asthma and 32 healthy control subjects. Each dataset was analyzed separately, followed by meta-analysis of differentially expressed genes (DEGs). Heterogenicity assessment, pathway enrichment and Single-sample Gene Set Enrichment Analysis were performed. Differentially expressed genes were further matched with genome-wide association studies (GWAS) of asthma. Results This study identified 150 genes that were consistently dysregulated in asthma-derived ASM cells compared to healthy control. NLRP2 showed the greatest upregulation in asthma as measured by pooled log2 fold change (effect size) in asthma, whereas ABI3 was the most downregulated. Pathway analysis highlighted prominent perturbation of IL-4 and IL-13 signaling. Thirteen DEGs overlapped with loci reported earlier in GWAS asthma database, which further underscores our findings. Conclusions To the best of our knowledge this first meta-analysis of ASM transcriptomes delineates a core set of genes and pathways underlying asthma-related airway remodeling. These findings refine our understanding of ASM-specific molecular networks and may guide targeted therapeutics for asthma in future.