ArticleThe American journal of pathology2008
Factor Xa stimulates proinflammatory and profibrotic responses in fibroblasts via protease-activated receptor-2 activation.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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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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
60 citing papers in PubMed, 120 citations in OpenAlex.
- Neutrophil extracellular traps in cardiovascular disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Impact of mesenchymal stem cells on the coagulation mechanism in patients with liver cirrhosis: A review and prospects.Liver research (Beijing, China) · 2026Review
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- Role of Mast Cells and Their Mediators in Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Significance of FXa and its receptor PAR2 for the growth of colon cancer cellsFrontiers in oncology · 2025Article
- Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.Biomolecules · 2024Review
- Update on protease-activated receptor 2 in inflammatory and autoimmune dermatological diseases.Frontiers in immunology · 2024Review
- Xa inhibitor edoxaban ameliorates hepatic ischemia-reperfusion injury via PAR-2-ERK 1/2 pathway.PloS one · 2024Article
- Article
- Article
- Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy.Life (Basel, Switzerland) · 2023Review
- Lysyl oxidase like-2 in fibrosis and cardiovascular disease.American journal of physiology. Cell physiology · 2023Review
- Lysyl oxidase-like 2 processing by factor Xa modulates its activity and substrate preference.Communications biology · 2023Article
- Resolving the conflicts around Par2 opposing roles in regeneration by comparing immune-mediated and toxic-induced injuries.Inflammation and regeneration · 2022Article
- Myocardial interaction of apixaban after experimental acute volume overload.The Journal of international medical research · 2022Article
- Alboserpin, the Main Salivary Anticoagulant from the Disease VectorImmunoHorizons · 2022Article
- The Therapeutic Potential of Anticoagulation in Organ Fibrosis.Frontiers in medicine · 2022Review
- Article
- Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Plasma Kallikrein as a Modulator of Liver Injury/Remodeling.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coagulation proteases have been suggested to play a role in the pathogenesis of tissue remodeling and fibrosis. We therefore assessed the proinflammatory and fibroproliferative effects of coagulation protease factor (F)Xa. We show that FXa elicits a signaling response in C2C12 and NIH3T3 fibroblasts. FXa-induced ERK1/2 phosphorylation was dependent on protease-activated receptor (PAR)-2 cleavage because desensitization with a PAR-2 agonist (trypsin) but not a PAR-1 agonist (thrombin) abolished FXa-induced signal transduction and PAR-2 siRNA abolished FXa-induced ERK1/2 phosphorylation. The PAR-2-dependent cellular effects of FXa led to fibroblast proliferation, migration, and differentiation into myofibroblasts, as demonstrated by the expression of alpha-smooth muscle actin and desmin, followed by the secretion of the cytokines monocyte chemotactic protein-1 and interleukin-6 as well as the expression of the fibrogenic proteins transforming growth factor-beta and fibronectin. To assess the relevance of FXa-induced proliferation and cell migration, we examined the effect of FXa in a wound scratch assay. Indeed, FXa facilitated wound healing in a PAR-2- and ERK1/2-dependent manner. Taken together, these results support the notion that, beyond its role in coagulation, FXa-dependent PAR-2 cleavage might play a role in the progression of tissue fibrosis and remodeling.
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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.