METTL3 promotes the hypertrophic scar fibrosis via m6A RNA methylation of GRAMD1B mRNA.

Hypertrophic scarring (HS) is a common fibrotic disorder characterized by excessive extracellular matrix deposition and fibroblast proliferation. N6-methyladenosine (m6A) RNA methylation, mediated by METTL3, has emerged as a critical regulator of gene expression and cellular processes. This study investigates the role of METTL3-mediated m6A methylation in hypertrophic scar fibrosis. We found that METTL3 expression and m6A RNA methylation levels were significantly elevated in human hypertrophic scar tissues and TGF-β1-induced human dermal fibroblasts. Silencing METTL3 reduced m6A methylation, impaired fibroblast proliferation, and decreased the mRNA and protein expression of fibrotic markers (ACTA2, Col1a1, Col3a1, and CTGF). Bioinformatics analysis identified GRAMD1B as a key differentially expressed gene in HS tissues. METTL3-mediated m6A methylation enhanced GRAMD1B mRNA stability, promoting its expression. These findings suggest that METTL3 contributes to hypertrophic scar fibrosis by regulating m6A methylation of GRAMD1B mRNA, highlighting METTL3 as a potential therapeutic target for fibrotic disorders.