ArticleProceedings of the National Academy of Sciences of the United States of America2019
Triggering of a Dll4-Notch1 loop impairs wound healing in diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
- The Role of the Notch1 Signaling Pathway in the Pathogenesis and Treatment of Diabetic Foot: A Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Review
- ATF7 drives diabetic wound healing via NOTCH1 repression and N1ICD-dependent macrophage polarization control.JCI insight · 2026Article
- Single-cell transcriptomics-guided dynamic hydrogel delivery of artemisia argyi-derived EVs relieves ER stress and promotes diabetic wound regeneration.Journal of nanobiotechnology · 2026Article
- Wound Healing and Angiogenic Profiling of Dermal Endothelial Cells Isolated From People With Type 2 Diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Roles of efferocytosis in wound repair: Process, cells, and signals.Genes & diseases · 2026Review
- Ononin-modified Chitosan/β-glycerophosphate hydrogel-loaded adipose-derived stem cells promote the repair of diabetic wounds in rats.BMC biotechnology · 2026Article
- The effect of medication use on chronic pruritus in patients with type 2 diabetes mellitus: a multicenter cross-sectional study.Scientific reports · 2026Article
- Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers.Journal of diabetes · 2026Review
- Hypothesis: Stem Cells Improve Skin Rejuvenation Through Multiple Signaling Pathways.Stem cell reviews and reports · 2026Review
- Endothelial cells regulate mesangial cells through the Dll4/Notch3 axis to participate in glomerular injury in lupus nephritis.Frontiers in immunology · 2026Article
- Multimodal Bioactive Approaches in Smart Dressings for Diabetic Foot Ulcers.International journal of nanomedicine · 2026Review
- Shengji ointment accelerates diabetic foot ulcer wound healing by regulating inflammatory microenvironment.Frontiers in pharmacology · 2026Article
- Revolutionizing Diabetic Foot Ulcer Management: Exploring the Therapeutic Potential of Natural Products.Current pharmaceutical design · 2026Review
- Optimizing adipose-derived stem cell therapy for diabetic foot ulcers.World journal of diabetes · 2025Article
- Potential roles of histone deacetylases in diabetic wound healing.World journal of diabetes · 2025Review
- A Clinical Decision Support Tool for the Management of Diabetes-Related Foot Ulcers (DRFUs) Using a Topical Haemoglobin Spray.International wound journal · 2025Review
- Exosomes from MicroRNA-125b-Modified Adipose-Derived Stem Cells Promote Wound Healing of Diabetic Foot Ulcers.Current stem cell research & therapy · 2025Article
- Angiogenesis during diabetic wound repair: from mechanism to therapy opportunity.Burns & trauma · 2025Review
- Roxadustat: A catalyst for diabetic wound healing through re-epithelialization and angiogenesis.CytoJournal · 2025Article
- Liver Fluke-Derived Molecules Accelerate Skin Repair Processes in a Mouse Model of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic foot ulcerations (DFUs) represent a major medical, social, and economic problem. Therapeutic options are restricted due to a poor understanding of the pathogenic mechanisms. The Notch pathway plays a pivotal role in cell differentiation, proliferation, and angiogenesis, processes that are profoundly disturbed in diabetic wounds. Notch signaling is activated upon interactions between membrane-bound Notch receptors (Notch 1-4) and ligands (Jagged 1-2 and Delta-like 1, 3, 4), resulting in cell-context-dependent outputs. Here, we report that Notch1 signaling is activated by hyperglycemia in diabetic skin and specifically impairs wound healing in diabetes. Local inhibition of Notch1 signaling in experimental wounds markedly improves healing exclusively in diabetic, but not in nondiabetic, animals. Mechanistically, high glucose levels activate a specific positive Delta-like 4 (Dll4)-Notch1 feedback loop. Using loss-of-function genetic approaches, we demonstrate that Notch1 inactivation in keratinocytes is sufficient to cancel the repressive effects of the Dll4-Notch1 loop on wound healing in diabetes, thus making Notch1 signaling an attractive locally therapeutic target for the treatment of DFUs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.