Asthma is regarded as a common pulmonary disease among the pediatric population, and the incidence and mortality rates have recently been found to increase significantly, making it one of the critical chronic, life-threatening diseases (Basharat et al., 2018, Kercsmar and Shipp, 2019, Moral et al., 2019). Recently published reports suggest the etiology of asthma is associated with airway inflammation and remodeling (Haktanir Abul et al., 2019, Hoch et al., 2019), where excessive proliferation and migration of airway smooth muscle cells (ASMCs) are pivotal factors for airway remodeling in asthma (Kume, 2021). The ASMCs are stimulated during airway remodeling by external signals, including growth factors exacerbated by inflammatory transmitters-induced airway hyperplasia, hypertrophy and contraction, cytokines release, and protease production (James et al., 2018). Therefore, preventing the excessive proliferation and migration of ASMCs is the key to treating asthma.

Human β defensin 3 (HBD-3) is an antibacterial peptide with a size of 4–5 kDa produced by the human body (Inthanachai et al., 2021), comprising 45 amino acids, and possesses broad-spectrum and potent antimicrobial activity, particularly effective against Gram-positive bacterial like Staphylococcus aureus (Fusco et al., 2021). The HBD-3, being a natural antibacterial peptide, is mainly expressed in mammalian skin and mucosal epithelial cells (Bauer et al., 2013). It has been recently reported that HBD-3 plays a vital role in regulating immune inflammatory response and wound repair (Hirsch et al., 2009, Xia et al., 2014). Similarly, hBD family members have also been found to participate in asthma progression in multiple ways, e.g., hBD1 was demonstrated to promote asthma development (Levy et al., 2005), while hBD-2 showed a protective role in asthma (Pinkerton et al., 2021). Similarly, HBD-3 was found to be highly expressed in asthmatic patients and promote the interleukin-8 (IL-8) production of ASMCs through regulating the ERK1/2 MAPK pathway, which first demonstrated the pro-inflammatory role of HBD-3 in asthma (Wang et al., 2017b). However, the effects of HBD-3 on the excessive proliferation and migration of ASMCs induced by platelet-derived growth factor-BB (PDGF-BB) have not been reported.

RNA modification significantly affects the structure, function, and stability of RNA, making it a research hotspot in recent years. Among all RNA modifications, N6 methyladenosine (m6A) is the most common and most studied modification in eukaryotic mRNA (Chen and Wong, 2020). Methyltransferase like 3 (METTL3), as the core of methyltransferase complex promoting m6A modification, has been reported to promote m6A modification of RNA, mediate RNA posttranscriptional metabolism, and participate in the pathological process of many diseases (Zhang et al., 2020). It can also induce abnormal m6A modification in a variety of tumors and promote tumorous cell proliferation, including gastric (Wang et al., 2020) and colorectal cancer cells (Chen et al., 2021). METTL3 in asthma has been found to regulate the proportion of Treg cells via modulating the m6A level and mRNA stability of Foxp3(Fan et al., 2022). However, it is unclear whether METTL3-mediated RNA methylation plays a regulatory role in the abnormal proliferation of ASMCs.

Therefore, this study aimed to investigate the specific mechanism of HBD-3 in asthma progression. It is hypothesized that HBD-3 silencing could inhibit the abnormal proliferation of ASMCs through METTL3-mediated m6A methylation modification.