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

• DOI: 10.4239/wjd.v16.i3.102126
• Publication Date: 2025-01-20T20:02:58Z
• Authors: Ren-Jie Xiao; Tian-Jiao Wang; Dan-Yin Wu; Shui-Fa Yang; Hai Gao; Pei-Dong Gan; Yang-Yan Yi; You-Lai Zhang
• Keywords: Viability assay; Masson's trichrome stain

BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes. N6-methyladenosine (m6A)-related epigenetic regulation widely involved the pathogenesis of diabetes complications. However, function m6A methyltransferase Wilms tumor 1-associated protein (WTAP) diabetic healing remains elusive. AIM To investigate potential regulatory mechanism WTAP during healing. METHODS Human umbilical vein endothelial cells (HUVECs) were induced high glucose (HG) to establish vitro cell model. Male BALB/c mice intraperitoneally injected streptozotocin mimic diabetes, full-thickness excision was made HG-induced HUVECs mouse models treated siRNAs DNA 1 (DNMT1) overexpression vectors. Cell viability migration ability detected by counting kit-8 Transwell assays. In angiogenesis measured using tube formation experiment. The images wounds captured, re-epithelialization collagen deposition skin tissues analyzed hematoxylin eosin staining Masson’s trichrome staining. RESULTS expression several methyltransferases, including METTL3, METTL14, METTL16, KIAA1429, WTAP, RBM15, measured. exhibited most elevation compared normal control. depletion notably restored enhanced suppressed HG. unclosed area smaller knockdown-treated than control at nine days post-wounding, along rate deposition. levels on DNMT1 mRNA repressed knockdown HUVECs. inhibited Overexpression reversed effects CONCLUSION elevated epigenetically regulates modification impair