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Related Concept Videos

Diabetic Foot Ulcer01:31

Diabetic Foot Ulcer

Definition A diabetic foot ulcer (DFU) is a chronic, non-healing wound that develops in individuals with diabetes. It typically occurs on pressure-bearing areas such as the heel, metatarsal heads, or hallux, and carries a high risk of infection and amputation.Pathophysiology • The development of DFUs can be explained by four interconnected mechanisms: neuropathy, ischemia, infection, and impaired wound healing. • Neuropathy is the most common factor. Sensory neuropathy reduces pain perception,...
Diabetic Neuropathy01:22

Diabetic Neuropathy

DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...

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Related Experiment Video

Updated: Jul 18, 2026

Creation and Transplantation of an Adipose-derived Stem Cell ASC Sheet in a Diabetic Wound-healing Model
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NETosis Delays Diabetic Wound Healing in Mice and Humans.

Gian Paolo Fadini1, Lisa Menegazzo2, Mauro Rigato3

  • 1Department of Medicine, University of Padova, Padova, Italy Venetian Institute of Molecular Medicine, Padova, Italy gianpaolo.fadini@unipd.it.

Diabetes
|January 8, 2016
PubMed
Summary

Neutrophil extracellular traps (NETs) and NETosis are elevated in diabetic foot ulcers (DFUs), delaying wound healing. Inhibiting protein arginine deiminase 4 (PAD4) improved healing in diabetic mice, suggesting NETosis is a therapeutic target for DFUs.

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Area of Science:

  • Immunology
  • Wound Healing
  • Diabetic Complications

Background:

  • Neutrophils release neutrophil extracellular traps (NETs) via NETosis, a process implicated in defense but also tissue damage.
  • In diabetes, neutrophils are primed for NETosis, potentially exacerbating diabetic foot ulcer (DFU) complications.

Purpose of the Study:

  • To investigate the role of NETosis in the pathophysiology and healing of diabetic foot ulcers (DFUs).

Main Methods:

  • Proteomic analysis of human DFUs, assessment of NET components in patient blood, and evaluation of neutrophil function in DFU patients.
  • In vivo studies in diabetic mice using intravital microscopy and PAD4 inhibition (Cl-amidine) to assess NETosis and wound healing.

Main Results:

  • NET components were enriched in nonhealing DFUs and elevated in the blood of DFU patients.
  • High neutrophil elastase in wounds correlated with infection and ulcer worsening; serum elastase predicted delayed healing.
  • Diabetic mice showed increased NETosis in wounds, which was reduced by PAD4 inhibition, leading to improved wound healing.

Conclusions:

  • NETosis is implicated in delayed healing of diabetic foot ulcers.
  • Elevated NET components in blood and wounds are associated with DFU severity and poor outcomes.
  • Inhibition of PAD4 represents a potential therapeutic strategy to improve DFU healing by reducing NETosis.