Work

Exploration of novel biomarkers of obese asthma using RNA sequencing in high-fat-fed asthmatic model mice

Year: 2025

Type: article

Abstract: BACKGROUND: Obese asthma is a specific phenotype of childhood asthma characterized by increased severity, decreased quality of life, and reduced treatment response. Herein, we applied transcriptomics to investigate biomarkers of obese asthma. METHODS: Mouse models of obesity and asthma were induced through high-fat diet (HFD) feeding and ovalbumin inhalation, respectively. RNA was extracted from lung samples from HFD-fed asthma, HFD-fed control, normal-fat diet (NFD)-fed asthma, and NFD-fed control mice. Transcriptome sequencing data were analyzed for quality control (QC), and differentially expressed genes (DEGs) were identified. From this list, candidate genes were obtained through intersections, followed by the construction of protein-protein interaction (PPI) networks to identify key genes. Subsequently, immune cell infiltration was analyzed across the different subgroups. Key genes were validated using Quantitative Polymerase Chain Reaction (PCR). RESULTS: Overall, 86 candidate genes were identified from the intersection of different DEG sets. PPI networks were constructed using three algorithms, revealing nine key genes (ITGM, Slc11a1, Nos2, PirB, IL1RN, LCN2, CD33, MSR1, and CXCL2). Immune infiltration analysis revealed distinct responses in immune cells, including naïve B cells and plasma cells. Following verification by qPCR, ITGAM, Nos2, LCN2, CD33, MSR1, and CXCL2 were confirmed to be significantly higher in the HFD-fed asthma group than in the NFD-fed asthma group. Slc11a1 was significantly downregulated, while PirB and IL1RN showed no significant differences. The expression levels of ITGAM, Nos2, and LCN2 demonstrated a consistent trend in human peripheral blood samples. However, to further substantiate their roles in obesity-associated asthma, an expanded sample size is required for confirmation. CONCLUSION: This study systematically investigated the molecular mechanisms underlying the associated obesity and metabolic disorders, identified biomarkers, and provided new directions for future therapeutic and clinical studies on obese asthma.

Source: Genomics

DOI: 10.1016/j.ygeno.2025.111115