ArticleThe Journal of biological chemistry2011
Activated protein C enhances human keratinocyte barrier integrity via sequential activation of epidermal growth factor receptor and Tie2.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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Who cites it
21 citing papers in PubMed, 51 citations in OpenAlex.
- Low circulating protein C levels are associated with lower leg ulcers in patients with diabetes.BioMed research international · 2013Trial
- Advances in the comprehensive mechanisms, diagnosis, and treatment of heatstroke-induced coagulopathy.Frontiers in cell and developmental biology · 2025Review
- Endothelial Protein C Receptor and 3K3A-Activated Protein C Protect Mice from Allergic Contact Dermatitis in a Contact Hypersensitivity Model.International journal of molecular sciences · 2024Article
- Effects of mucopolysaccharide polysulphate on tight junction barrier in human epidermal keratinocytes.Experimental dermatology · 2022Article
- Activated Protein C Protects against Murine Contact Dermatitis by Suppressing Protease-Activated Receptor 2.International journal of molecular sciences · 2022Article
- Article
- Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside.International journal of molecular sciences · 2019Review
- Lupeol, a Pentacyclic Triterpene, Promotes Migration, Wound Closure, and Contractile Effect In Vitro: Possible Involvement of PI3K/Akt and p38/ERK/MAPK Pathways.Molecules (Basel, Switzerland) · 2018Article
- Review
- Regulation of immune cell signaling by activated protein C.Journal of leukocyte biology · 2018Review
- Protein C receptor stimulates multiple signaling pathways in breast cancer cells.The Journal of biological chemistry · 2018Article
- Relationship between G proteins coupled receptors and tight junctions.Tissue barriers · 2018Review
- Activated protein C binds directly to Tie2: possible beneficial effects on endothelial barrier function.Cellular and molecular life sciences : CMLS · 2017Article
- 2016 Scientific Sessions Sol Sherry Distinguished Lecturer in Thrombosis: Thrombotic Stroke: Neuroprotective Therapy by Recombinant-Activated Protein C.Arteriosclerosis, thrombosis, and vascular biology · 2016Review
- Activated protein C: biased for translation.Blood · 2015Review
- Article
- Activated protein C: A regulator of human skin epidermal keratinocyte function.World journal of biological chemistry · 2014Review
- Article
- Protein C anticoagulant and cytoprotective pathways.International journal of hematology · 2012Review
- Barrier stabilizing mediators in regulation of microvascular endothelial permeability.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2012Review
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keratinocytes play a critical role in maintaining epidermal barrier function. Activated protein C (APC), a natural anticoagulant with anti-inflammatory and endothelial barrier protective properties, significantly increased the barrier impedance of keratinocyte monolayers, measured by electric cell substrate impedance sensing and FITC-dextran flux. In response to APC, Tie2, a tyrosine kinase receptor, was rapidly activated within 30 min, and relocated to cell-cell contacts. APC also increased junction proteins zona occludens, claudin-1 and VE-cadherin. Inhibition of Tie2 by its peptide inhibitor or small interfering RNA abolished the barrier protective effect of APC. Interestingly, APC did not activate Tie2 through its major ligand, angiopoietin-1, but instead acted by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor. Furthermore, when activation of Akt, but not ERK, was inhibited, the barrier protective effect of APC on keratinocytes was abolished. Thus, APC activates Tie2, via a mechanism requiring, in sequential order, the receptors, endothelial protein C receptor, protease-activated receptor-1, and EGF receptor, which selectively enhances the PI3K/Akt signaling to enhance junctional complexes and reduce keratinocyte permeability.
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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.