ArticleJCI insight2025
Endothelial FOXM1 and Dab2 promote diabetic wound healing.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- A novel preclinical strategy for diabetic wound: CITED2-loaded hydrogel spray targeted macrophage reprogramming.Journal of nanobiotechnology · 2026Article
- Agonal cell resuscitation strategy to promote tissue repair.Nature communications · 2026Article
- Sustained-release CGRP microspheres accelerate diabetic wound healing by synergistically promoting neurovascular regeneration through modulation of macrophage and endothelial cell functions.Materials today. Bio · 2026Article
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Microbial allies in skin trauma recovery: from immune modulation to engineered probiotic therapeutics.Burns & trauma · 2026Review
- SIRT6 Overexpression Enhances Diabetic Foot Ulcer Healing via Nrf2 Pathway Activation.Inflammation · 2025Article
- Research progress on the role and mechanisms of ferroptosis in diabetic wound repair.Cell death discovery · 2025Review
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Authors and funding
16 authors.
Funding
Abstract
Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor-dependent (VEGF-dependent) angiogenesis remain unclear. In our study, the molecular underpinnings of endothelial dysfunction in diabetes are investigated, focusing on the roles of disabled-2 (Dab2) and Forkhead box M1 (FOXM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high-glucose-treated primary mouse skin endothelial cells. In diabetic mice with endothelial deficiency of Dab2, in vivo and in vitro angiogenesis and wound healing were reduced when compared with wild-type diabetic mice. Restoration of Dab2 expression by injected mRNA-containing, LyP-1-conjugated lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. Furthermore, FOXM1 was downregulated in skin endothelial cells under high-glucose conditions as determined by RNA-sequencing analysis. FOXM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FOXM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. Our study provides evidence of the crucial roles of Dab2 and FOXM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.
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Registered trials
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