ArticleEuropean journal of immunology2025
Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps-Fibroblast Crosstalk.
Article in European journal of immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026Review
- Emerging evidence of neutrophil extracellular traps in essential hypertension and target organ damage: pathophysiological insights and therapeutic implications.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Neutrophil extracellular traps in post-traumatic urethral microenvironment promote hypertrophic urethral stricture via the TLR9/NF-kB/Smad3/IL-8 axis.Apoptosis : an international journal on programmed cell death · 2026Article
- Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.iScience · 2026Review
- Regenerative Therapies for Cosmetic Dermatology for Patients with Diabetes Mellitus: Skin Aging, Aesthetic Concerns, and Evidence-Based Best Practices.International journal of molecular sciences · 2026Review
- Development of a new biological dressing: the modified cross-linking of Chitosan derived from cuttlefish (Sepia pharaonis) by-products as an effective agent for promoting cell migration.Bioresources and bioprocessing · 2026Article
- Neutrophil Extracellular Traps in Wound Healing of Diabetes: Mechanisms, Inducers, and Therapeutic Implications.Mediators of inflammation · 2026Review
- Stem Cell Based Regenerative Applications for the Management of Diabetes Induced Systemic Complications.Stem cell reviews and reports · 2026Review
- Article
- The Role of Systemic Immune-Inflammation Index and Prognostic Nutritional Index in Predicting Outcomes of Chinese Patients with Diabetic Foot Ulcers After Moist Exposed Burn Ointment Treatment.International journal of general medicine · 2026Article
- Immune cells in diabetic wound repair: the key to better wound management.Frontiers of medicine · 2025Review
- Hyperglycemia Modulates the Expression of MAPK13, TSP1, and CXCR2 During Wound Healing in Sprague Dawley Rats.Biology · 2025Article
- Neutrophil Extracellular Traps (NETs) in health and disease.Molecular biomedicine · 2025Review
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Macrophage and inflammation in diabetes and metabolic dysfunction-associated steatotic liver disease: From mechanisms to therapeutic strategies.World journal of diabetes · 2025Review
- Developing models for the diagnosing of ulcerative colitis and prognosis of anti-TNF-α non-response based on neutrophil extracellular trap-associated genes.Frontiers in immunology · 2025Article
- Targeting immune cell migration as therapy for inflammatory disease: a review.Frontiers in immunology · 2025Review
- Neutrophil-Fibroblast Crosstalk Drives Immunofibrosis in Sequelae of Pelvic Inflammatory Disease Through Neutrophil Extracellular Traps.Mediators of inflammation · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophils interact with and activate fibroblasts through the release of neutrophil extracellular traps (NETs). We investigated the role of NETs-fibroblast crosstalk in the cutaneous wound healing of type 2 diabetes (T2D). Neutrophils/NETs, serum, and primary human skin fibroblasts (HSFs) were obtained from individuals with T2D and age/sex-matched controls. NET-stimulation studies were performed on neutrophils/HSFs, with and without specific inhibitors, while HSF healing capacity was assessed using a scratch wound healing assay. T2D HSFs display a profibrotic phenotype, showing increased CCN2/CTGF, α-smooth muscle actin, and collagen release, albeit with impaired healing capacity, elevated type I collagen C-terminal telopeptide, and collagen degradation associated with increased (∼3.5-fold) matrix metalloproteinase-9 (MMP-9) in T2D neutrophils/NETs. IL-8 induced the expression of MMP-9 in neutrophils/NETs. Moreover, T2D neutrophils/NETs exhibited increased IL-8 content, which acted in an autocrine/paracrine fashion to further augment its production by neutrophils/HSFs. The findings were validated in normoglycemic individuals during a hyperglycemic clamp with concomitant lipid infusion and further corroborated immunohistochemically in diabetic plantar ulcer biopsies. This novel, vicious circle of NETs/interleukin-8/MMP-9/HSFs was hindered by IL-8 or MMP-9 blockade via specific inhibitors or by dismantling the NET-scaffold with DNase I, suggesting candidate therapeutic targets in wound healing impairment of T2D.
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Registered trials
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 Socratic graph.