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N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through

Ren-Jie Xiao1, Tian-Jiao Wang2,3, Dan-Yin Wu4

  • 1Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College of Nanchang University, Nanchang 330006, Jiangxi Province, China.

World Journal of Diabetes
|March 17, 2025
PubMed
Abstract

Insights

Wilms tumor 1-associated protein (WTAP) is elevated in high glucose conditions and impairs diabetic wound healing by epigenetically modifying DNA methyltransferase 1 (DNMT1). Reducing WTAP improves cell viability, migration, and wound closure.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Diabetology

Background:

  • Diabetic wound healing is a major clinical challenge.
  • N6-methyladenosine (m6A) epigenetic regulation is implicated in diabetes complications.
  • The role of WTAP in diabetic wound healing is not well understood.

Purpose of the Study:

  • To investigate the epigenetic regulatory role of WTAP in diabetic wound healing.
  • To elucidate the mechanism by which WTAP influences diabetic wound repair.

Main Methods:

  • Established in vitro (high glucose-induced HUVECs) and in vivo (streptozotocin-induced diabetic mice) models.
  • Utilized WTAP siRNA and DNMT1 overexpression vectors for manipulation.
  • Assessed cell viability, migration, angiogenesis, re-epithelialization, and collagen deposition.

Main Results:

  • WTAP expression was significantly upregulated in high glucose conditions.
  • WTAP depletion restored HUVEC viability, migration, and angiogenesis.
  • WTAP knockdown accelerated wound healing, enhancing re-epithelialization and collagen deposition in mice.
  • WTAP epigenetically regulated m6A modification of DNMT1, inhibiting its expression and function.

Conclusions:

  • Elevated WTAP expression impairs diabetic wound healing.
  • WTAP epigenetically modifies DNMT1, contributing to the pathogenesis of diabetic complications.
  • Targeting WTAP may offer a therapeutic strategy for improving diabetic wound healing.
Keywords:
DNA methyltransferase 1Diabetic wound healingHuman umbilical vein endothelial cellsN6-methyladenosineWilms tumor 1-associated protein

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