Clinical and laboratory study reveals that negative pressure wound therapy restores WTAP expression in diabetic foot ulcers, suggesting m6A RNA methylation enhances wound healing.
Key Points
To determine the role of the RNA m6A methyltransferase WTAP in facilitating diabetic foot ulcer repair during negative pressure wound therapy.
Analyzed wound margin tissue samples from 46 diabetic foot ulcer patients and 16 non-diabetic chronic ulcer patients before and after one week of negative pressure wound therapy to measure total m6A and methyltransferase (METTL3, METTL14, WTAP) expression.
Used high glucose-induced HaCaT keratinocyte and human dermal fibroblast cell models exposed to an in vitro negative pressure system with WTAP knockdown to evaluate proliferation and migration.
Baseline tissue levels of METTL3, METTL14, WTAP, and total m6A were significantly lower in diabetic ulcers than in non-diabetic chronic ulcers, but all significantly increased following one week of negative pressure wound therapy.
Upregulation of WTAP following therapy demonstrated a significant positive correlation with total m6A levels and with 4-week wound healing outcomes in diabetic foot ulcer patients.
In vitro negative pressure reversed high glucose-induced WTAP suppression, whereas WTAP knockdown substantially inhibited keratinocyte and fibroblast proliferation and migration.