ArticleProceedings of the National Academy of Sciences of the United States of America2011
Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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Who cites it
47 citing papers in PubMed, 85 citations in OpenAlex.
- Angiogenesis in Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multi-omic mapping of Drosophila protein secretomes reveals tissue-specific origins and inter-organ trafficking.Nature communications · 2026Article
- Autoantibodies against endothelial protein C receptor and integrin αvβ6 predict the development of ulcerative colitis.Journal of gastroenterology · 2025Article
- Newly developed evaluation for intestinal permeability usingJournal of clinical biochemistry and nutrition · 2025Article
- Genetic susceptibility to recurrent vulvovaginal candidiasis in an African population from Nairobi, Kenya.Scientific reports · 2025Article
- Endothelial Protein C Receptor: A Multifunctional Mediator in the Pathophysiology of Rheumatoid Arthritis.Cells · 2025Review
- Tissue factor-dependent colitogenic CD4Nature communications · 2025Article
- A Novel Murine Model Enabling rAAV8-PC Gene Therapy for Severe Protein C Deficiency.International journal of molecular sciences · 2024Article
- 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
- Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation.JMA journal · 2023Review
- Contribution of Blood Vessel Activation, Remodeling and Barrier Function to Inflammatory Bowel Diseases.International journal of molecular sciences · 2023Review
- Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives.Journal of clinical medicine · 2023Article
- Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases.World journal of gastroenterology · 2023Review
- Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn's Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition.Cellular and molecular gastroenterology and hepatology · 2023Article
- Dysregulated haemostasis in thrombo-inflammatory disease.Clinical science (London, England : 1979) · 2022Review
- Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer.Inflammatory bowel diseases · 2022Article
- Leaky Gut in IBD: Intestinal Barrier-Gut Microbiota Interaction.Journal of microbiology and biotechnology · 2022Review
- Selegiline Protects Against Lipopolysaccharide (LPS)-Induced Impairment of the Blood-Brain Barrier Through Regulating the NF-κB/MLCK/p-MLC Signaling Pathway.Neurotoxicity research · 2022Article
- Progesterone differentially affects the transcriptomic profiles of cow endometrial cell types.BMC genomics · 2022Article
- Venous and arterial thromboembolism in patients with inflammatory bowel diseases.World journal of gastroenterology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The protein C (PC) pathway is a well-characterized coagulation system. Endothelial PC receptors and thrombomodulin mediate the conversion of PC to its activated form, a potent anticoagulant and anti-inflammatory molecule. Here we show that the PC pathway is expressed on intestinal epithelial cells. The epithelial expression of PC and endothelial PC receptor is down-regulated In patients with inflammatory bowel disease. PC(-/-)/PC(Tg) mice, expressing only 3% of WT PC, developed spontaneous intestinal inflammation and were prone to severe experimental colitis. These mice also demonstrated spontaneous elevated production of inflammatory cytokines and increased intestinal permeability. Structural analysis of epithelial tight junction molecules revealed that lack of PC leads to decreased JAM-A and claudin-3 expression and an altered pattern of ZO-1 expression. In vitro, treatment of epithelial cells with activated PC led to protection of tight junction disruption induced by TNF-α, and in vivo, topical treatment with activated PC led to mucosal healing and amelioration of colitis. Taken together, these findings demonstrate that the PC pathway is a unique system involved in controlling intestinal homeostasis and inflammation by regulating epithelial barrier function.
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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.