METTL3 destabilizes RFX7 to ameliorate PDGF-BB-induced airway smooth muscle cell dysfunction and inflammation in an in vitro model of childhood asthma

Background Childhood asthma represents a significant global health burden, characterized by chronic airway inflammation and remodeling. Regulatory factor X7 (RFX7) has emerged as a potential key player in asthma pathogenesis. However, its specific role in modulating airway smooth muscle cell (ASMC) dysfunction—a hallmark of asthma pathology—remains poorly understood.Methods An in vitro asthma model was established by stimulating airway smooth muscle cells (ASMCs) with platelet-derived growth factor-BB (PDGF-BB). Quantitative real-time PCR (qRT-PCR) and Western blotting were employed to measure the mRNA and protein expression levels of RFX7 and METTL3, respectively. Functional assays, including 5-ethynyl-2’-deoxyuridine incorporation, Transwell, and wound-healing assays, were utilized to evaluate ASMC proliferation, invasion, and migration. Inflammatory responses were assessed by enzyme-linked immunosorbent assays (ELISAs) targeting interleukin-6 (IL-6).Results RFX7 expression levels were significantly elevated in the serum of pediatric asthma patients and in PDGF-BB-induced ASMCs, whereas METTL3 expression was downregulated. PDGF-BB stimulation enhanced ASMC proliferation, invasion, and migration, all of which were markedly attenuated by RFX7 knockdown. Furthermore, RFX7 deficiency reduced PDGF-BB-induced production of IL-6, TNF-α, ROS, and MDA, as well as the proportion of CD86-positive macrophages. Notably, METTL3 exhibited a negative correlation with RFX7 in patient sera and destabilized RFX7 transcripts in a YTHDF2-dependent manner. Consequently, overexpression of METTL3 alleviated PDGF-BB-induced ASMC dysfunction by downregulating RFX7.Conclusion METTL3-mediated destabilization of RFX7 ameliorated PDGF-BB-induced ASMC proliferation, migration, and invasion, while simultaneously suppressing inflammation, oxidative stress, and macrophage polarization. Targeting this METTL3-RFX7 axis may offer a novel therapeutic strategy to mitigate airway remodeling and inflammation in childhood asthma.