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

Area of Science:

• Molecular Biology
• Dermatology
• Epigenetics

Background:

• Hypertrophic scarring (HS) involves excessive extracellular matrix deposition and fibroblast proliferation.
• N6-methyladenosine (m6A) RNA methylation, regulated by METTL3, is crucial for gene expression and cellular functions.

Purpose of the Study:

• To investigate the role of METTL3-mediated m6A RNA methylation in hypertrophic scar fibrosis.
• To explore METTL3 as a potential therapeutic target for fibrotic disorders.

Main Methods:

• Analysis of METTL3 expression and m6A levels in human hypertrophic scar tissues and fibroblasts.
• Silencing METTL3 to assess its impact on fibroblast proliferation and fibrotic marker expression.
• Bioinformatics analysis to identify differentially expressed genes, including GRAMD1B.

Main Results:

• METTL3 expression and m6A RNA methylation were significantly increased in hypertrophic scar tissues and TGF-β1-induced fibroblasts.
• METTL3 silencing reduced m6A methylation, fibroblast proliferation, and fibrotic markers (ACTA2, Col1a1, Col3a1, CTGF).
• METTL3-mediated m6A methylation enhanced GRAMD1B mRNA stability, promoting its expression in HS.

Conclusions:

• METTL3 plays a significant role in hypertrophic scar fibrosis through m6A methylation of GRAMD1B mRNA.
• METTL3 inhibition presents a potential therapeutic strategy for managing hypertrophic scarring and other fibrotic conditions.