ArticleThe Journal of clinical investigation2018
Factor XII and uPAR upregulate neutrophil functions to influence wound healing.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Factor XII-A New Therapeutic Target? A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Cold-Induced Urticarias with Familial Background: Clinical Spectrum, Pathogenesis, and Diagnostic Challenges.Diagnostics (Basel, Switzerland) · 2025Review
- BDKRB1 activation induces CXCR2 desensitization in neutrophils during severe sepsis and exacerbates disease severity.JCI insight · 2025Article
- Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction.Cellular and molecular life sciences : CMLS · 2025Article
- Insights from the Evolution of Coagulation: A New Perspective on Anti-Inflammatory Strategies in the ICU-Focus on the Contact Activation System.Biomedicines · 2025Review
- Review
- Emerging pathways in thromboinflammation of sickle cell disease: novel findings in disease pathogenesis.Research and practice in thrombosis and haemostasis · 2025Review
- Pattern recognition receptor-associated immuno-thrombotic transcript changes in platelets and leukocytes with COVID19.PLoS pathogens · 2025Article
- Article
- Advancements in research on the thrombo-inflammation mechanisms mediated by factor XII in ischemic stroke.Journal of thrombosis and thrombolysis · 2025Review
- Article
- The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing.Clinical and translational medicine · 2025Article
- Non-classical neutrophil extracellular traps induced by PAR2-signaling proteases.Cell death & disease · 2025Article
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- Skin immunity and inflammation: cellular interactions and communication.Clinical & translational immunology · 2025Review
- A single-domain antibody targeting factor XII inhibits both thrombosis and inflammation.Nature communications · 2024Article
- Factor XII signaling via uPAR-integrin β1 axis promotes tubular senescence in diabetic kidney disease.Nature communications · 2024Article
- Factor XII promotes the thromboinflammatory response in a rat model of venoarterial extracorporeal membrane oxygenation.The Journal of thoracic and cardiovascular surgery · 2024Article
- Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.RSC advances · 2024Review
- uPAR (PLAUR) Marks Two Intra-Tumoral Subtypes of Glioblastoma: Insights from Single-Cell RNA Sequencing.International journal of molecular sciences · 2024Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 7 institutions in 3 countries.
Funding
Abstract
Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor-mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474). Downstream of pAkt2S474, FXII stimulation of neutrophils upregulated surface expression of αMβ2 integrin, increased intracellular calcium, and promoted extracellular DNA release. The sum of these activities contributed to neutrophil cell adhesion, migration, and release of neutrophil extracellular traps in a process called NETosis. Decreased neutrophil signaling in F12-/- mice resulted in less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did not affect neutrophil migration, whereas WT BM transplanted into F12-/- hosts was sufficient to correct the neutrophil migration defect in F12-/- mice and restore wound inflammation. Importantly, these activities were a zymogen FXII function and independent of FXIIa and contact activation, highlighting that FXII has a sophisticated role in vivo that has not been previously appreciated.
Indexed as
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What OpenQuestion holds
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 OpenQuestion graph.