m6A hypomethylation assembles a fibrogenic TCF7L2–Smad2/3 complex in pterygium

A) deposition on TCF7L2, Smad2, and Smad3 transcripts, impairing YTHDF2-mediated recognition and degradation, leading to their abnormal stabilization and subsequent protein accumulation. Elevated TCF7L2 partners with Smad2/3 to form a transcriptional complex that directly binds to the FN1 and COL1A1 promoters, driving their expression and extracellular matrix deposition. Exogenous modulation of METTL3 expression either mimics or reverses the TGF-β1-induced fibrotic phenotypes both in vitro and in vivo. Our findings reveal a mechanism through which environmental factors influence pterygium progression by modulating the formation of fibrotic transcriptional complexes via epitranscriptomic regulation. These insights offer potential avenues for treating fibrosis by targeting the epitranscriptome or specific transcriptional complexes.