ArticleJournal of cellular physiology2010
Thrombin down-regulates the TGF-beta-mediated synthesis of collagen and fibronectin by human proximal tubule epithelial cells through the EPCR-dependent activation of PAR-1.
Article in Journal of cellular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- The Influence of PAR 1 and Endothelin 1 on the Course of Specific Kidney Diseases.Journal of clinical medicine · 2025Article
- Human endothelial colony forming cells (ECFCs) require endothelial protein C receptor (EPCR) for cell cycle progression and angiogenic activity.Angiogenesis · 2025Article
- The Influence of Anti-PAR 1 and Anti-ACE 2 Antibody Levels on the Course of Specific Glomerulonephritis Types.Journal of clinical medicine · 2025Article
- Article
- Interaction of estradiol and renin-angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-β/smad signaling pathway.Molecular biology reports · 2024Review
- Article
- A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia.PloS one · 2023Article
- Emergent White Matter Degeneration in the rTg-DI Rat Model of Cerebral Amyloid Angiopathy Exhibits Unique Proteomic Changes.The American journal of pathology · 2022Article
- Hirudin, a thrombin inhibitor, attenuates TGF-β-induced fibrosis in renal proximal tubular epithelial cells by inhibition of protease-activated receptor 1 expression via S1P/S1PR2/S1PR3 signaling.Experimental and therapeutic medicine · 2022Article
- Comparative transcriptomic profiling of myxomatous mitral valve disease in the cavalier King Charles spaniel.BMC veterinary research · 2020Article
- Protease-activated receptor-1 contributes to renal injury and interstitial fibrosis during chronic obstructive nephropathy.Journal of cellular and molecular medicine · 2019Article
- Signaling Crosstalk of TGF-β/ALK5 and PAR2/PAR1: A Complex Regulatory Network Controlling Fibrosis and Cancer.International journal of molecular sciences · 2018Review
- Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice.Scientific reports · 2016Article
- Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH).Scientific reports · 2016Article
- The emerging role of coagulation proteases in kidney disease.Nature reviews. Nephrology · 2016Review
- Organ-specific protection against lipopolysaccharide-induced vascular leak is dependent on the endothelial protein C receptor.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.PloS one · 2013Article
- The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling.Cellular and molecular life sciences : CMLS · 2012Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Human proximal tubule (HK-2) cells are commonly used as cellular models to understand the mechanism by which inflammatory mediators cause renal injury. It has been observed that thrombin stimulates the expression of TGF-beta, extracellular matrix (ECM) proteins and proinflammatory cytokines by HK-2 cells. These in vitro responses correlate well with the pathology of glomerular and tubular diseases observed in acute renal injury. HK-2 cells express PAR-1 and the thrombin activation of this receptor has been reported to up-regulate the TGF-beta-mediated expression of ECM proteins, suggesting a possible pathogenic role for PAR-1 signaling by thrombin in acute renal injury. On the other hand, several recent studies have indicated that activated protein C plays a renoprotective role, thus inhibiting the inflammatory responses and attenuating renal injury, presumably by activating the same cell surface receptor. In this study, we show that HK-2 cells express endothelial protein C receptor (EPCR) and that the occupancy of this receptor by protein C switches the signaling specificity of thrombin so that the activation of PAR-1 by thrombin inhibits the TNF-alpha-mediated synthesis of IL-6 and IL-8 and down-regulates the TGF-beta-mediated expression of ECM proteins. These results suggest a possible protective role for EPCR in acute kidney injury.
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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.