Evidence mapPaperPMID 40170410Full record

ArticleEuropean journal of immunology2025

Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps-Fibroblast Crosstalk.

Dimitrios Tsilingiris, Anastasia-Maria Natsi, Efstratios Gavriilidis, Christina Antoniadou, Ioanna Eleftheriadou, Ioanna A Anastasiou, Anastasios Tentolouris, Evangelos Papadimitriou, Evgenios Eftalitsidis, Panagiotis Kolovos and 6 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026
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  9. Tissue barriers · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Dimitrios TsilingirisFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Anastasia-Maria NatsiLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Efstratios GavriilidisFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Christina AntoniadouFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Ioanna EleftheriadouFirst Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Ioanna A AnastasiouFirst Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Anastasios TentolourisFirst Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Evangelos PapadimitriouFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Evgenios EftalitsidisLaboratory of Cell Biology, Proteomics and Cell Cycle, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
Panagiotis KolovosFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Victoria TsironidouLaboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Alexandra GiatromanolakiDepartment of Pathology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Maria KoffaLaboratory of Cell Biology, Proteomics and Cell Cycle, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
Nikolaos TentolourisFirst Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.ORCID 0000-0002-6864-4289
Panagiotis SkendrosFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.
Konstantinos RitisFirst Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.ORCID 0000-0002-3366-5549

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Diabetes Mellitus, Type 2Extracellular TrapsFibroblastsInterleukin-8Matrix Metalloproteinase 9NeutrophilsWound HealingAgedCells, CulturedFemaleHumansMaleMiddle AgedSkinCXCL8 protein, humanInterleukin-8Matrix Metalloproteinase 9MMP9 protein, humaninterleukin‐8matrix metalloproteinase‐9neutrophil extracellular trapstype 2 diabetes mellituswound healing

Identifiers

PMID40170410
PMCPMC11962236

What Socratic holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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 Socratic graph.