What question did this study set out to answer?

To evaluate the role and clinical impact of neutrophil extracellular trap formation (NETosis) on the healing of diabetic foot ulcers in both human patients and mouse models.

January 6, 2016Diabetes

NETosis Delays Diabetic Wound Healing in Mice and Humans

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Authors

GFGian Paolo FadiniCross-Cutting Cardiology LMLisa MenegazzoUniversity of Padua MRMauro RigatoUniversity of Padua

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Implication

Translational study demonstrates that excessive NETosis impairs diabetic wound healing in mice and humans, indicating that targeting neutrophil extracellular traps may improve ulcer recovery.

Key Points

To evaluate the role and clinical impact of neutrophil extracellular trap formation (NETosis) on the healing of diabetic foot ulcers in both human patients and mouse models.
Analyzed wound tissue and circulating blood from diabetic foot ulcer patients using proteomics and biomarker validation assays to measure NET components such as neutrophil elastase.
Isolated peripheral neutrophils from patients with diabetic foot ulcers to evaluate rates of spontaneous and inducible NETosis.
Assessed skin PAD4 activity and wound-bed NETosis using intravital microscopy and flow cytometry in diabetic mice, followed by therapeutic testing with the PAD4 inhibitor Cl-amidine.
NET components, including neutrophil elastase, histones, and proteinase-3, were enriched in nonhealing human ulcers and circulating blood, with high serum elastase predicting delayed healing and ulcer worsening.
Circulating neutrophils from diabetic foot ulcer patients exhibited increased spontaneous NETosis alongside impaired inducible NETosis.
Diabetic mice displayed elevated cutaneous PAD4 activity and wound-bed NETosis, whereas pharmacological PAD4 inhibition with Cl-amidine reduced NETting neutrophils and rescued diabetic wound healing.

Cite This Study

Fadini et al. (2016) studied this question.

synapsesocial.com/papers/6a006032ef8139f8ff778e18 https://doi.org/10.2337/db15-0863

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Implication

Translational study demonstrates that excessive NETosis impairs diabetic wound healing in mice and humans, indicating that targeting neutrophil extracellular traps may improve ulcer recovery.

NETosis Delays Diabetic Wound Healing in Mice and Humans

Discussion

Member takes

Implication

Key Points

Cite This Study

NETosis Delays Diabetic Wound Healing in Mice and Humans

Discussion

Member takes

Implication

Key Points

Cite This Study

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