STM2457 is Therapeutic for Idiopathic Pulmonary Fibrosis by Inhibiting the METTL3-CTGF Signaling Axis

Methyltransferase-like 3 (METTL3) is integral in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The METTL3 antagonist STM2457 has demonstrated potential in mitigating fibrotic processes. However, the precise functions and mechanisms of STM2457 in IPF remain to be fully delineated. This research sought to elucidate the role and molecular mechanisms of STM2457 in IPF by developing an in vivo IPF model using C57BL/6 mice, wherein the IPF cohort received intraperitoneal injections of STM2457 at a dosage of 30 mg/kg. Our results indicate that STM2457 substantially diminishes fibroblast activity, alongside reducing collagen fiber deposition within pulmonary tissues, thereby significantly ameliorating lung pathology and functionality. Additionally, STM2457 markedly downregulated the expression levels of MET-TL3 and CTGF. Furthermore, overexpression of CTGF reversed the improving effect of STM2457 in IPF mice. Consequently, the METTL3 inhibitor STM2457 may mitigate fibroblast activity and enhance both pathological and functional outcomes in IPF by inhibiting the METTL3/CTGF signaling pathway.