ArticleThe American journal of pathology2011
Protease activated receptor-2 mediates activated protein C-induced cutaneous wound healing via inhibition of p38.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo-controlled, double-blind pilot clinical trial.International wound journal · 2015Trial
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Nanoencapsulated senotherapeutic compounds targeting connexin-43 for enhanced wound healing.iScience · 2026Article
- The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing.Clinical and translational medicine · 2025Article
- Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing.International journal of molecular sciences · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Article
- [Treatment failure after postinfectious purpura fulminans despite interdisciplinary surgical and intensive medical therapy].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2020Article
- Contribution of platelets, the coagulation and fibrinolytic systems to cutaneous wound healing.Thrombosis research · 2019Review
- Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside.International journal of molecular sciences · 2019Review
- Article
- Inflammation in Chronic Wounds.International journal of molecular sciences · 2016Review
- Activated protein C to heal pressure ulcers.International wound journal · 2016Article
- Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo.PloS one · 2016Article
- Hepatocyte growth factor activator inhibitor type 1 maintains the assembly of keratin into desmosomes in keratinocytes by regulating protease-activated receptor 2-dependent p38 signaling.The American journal of pathology · 2015Article
- Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring.Advances in wound care · 2015Review
- Activated protein C: A regulator of human skin epidermal keratinocyte function.World journal of biological chemistry · 2014Review
- Evaluation on potential contributions of protease activated receptors related mediators in allergic inflammation.Mediators of inflammation · 2014Review
- Activated protein C inhibits proliferation and tumor necrosis factor α-stimulated activation of p38, c-Jun NH2-terminal kinase (JNK) and Akt in rheumatoid synovial fibroblasts.Molecular medicine (Cambridge, Mass.) · 2013Article
- Mechanisms of anticoagulant and cytoprotective actions of the protein C pathway.Journal of thrombosis and haemostasis : JTH · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated protein C (APC) is a natural anticoagulant that exerts anti-inflammatory and cytoprotective properties mediated through the protease activated receptor (PAR)-1. APC can also proteolytically cleave PAR-2, although subsequent function is unknown. On the basis of recent evidence that APC promotes wound healing, the aim of this study was to determine whether APC acts through PARs to heal murine excisional wounds or to regulate human cultured keratinocyte function and to determine the signaling mechanisms. Topical administration of APC accelerated wound healing in wild-type mice and, unexpectedly, in PAR-1 knockout mice. PAR-2 knockout mice healed significantly slower than wild-type mice, and healing was not altered by adding APC, indicating that APC acts through PAR-2 to heal wounds. In cultured human primary keratinocytes, APC enhanced PAR-2, stimulated proliferation, activated phosphatidylinositol 3-kinase/Src/Akt, and inhibited phosphorylated (P)-p38. Inhibiting PAR-1 or PAR-2, by small-interfering RNA or blocking antibody, reversed APC-induced keratinocyte proliferation and Akt activation. Blocking PAR-2, but not PAR-1, reversed the inhibition of P-p38 by APC. Furthermore, inhibition of P-p38 accelerated wound healing in wild-type mice. In summary, although APC acts through both PAR-1 and PAR-2 to activate Akt and to increase keratinocyte proliferation, APC-induced murine wound healing depends on PAR-2 activity and inhibition of P-p38.
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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 OpenQuestion graph.