ArticleBlood2012
Cytoprotective signaling by activated protein C requires protease-activated receptor-3 in podocytes.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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.
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Who cites it
73 citing papers in PubMed, 126 citations in OpenAlex.
- Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study.Frontiers in immunology · 2021Trial
- Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Activated protein C ameliorates diabetes-induced atherosclerosis by sustaining macrophage efferocytosis.Cardiovascular diabetology · 2025Article
- P16-positive senescent cells promote DKD by the dysregulation of glycolysis and mitochondrial metabolism.Cell death discovery · 2025Article
- Serine proteases and protease-activated receptors signaling in the kidney.American journal of physiology. Cell physiology · 2025Review
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.Journal of thrombosis and haemostasis : JTH · 2024Article
- Review
- Endothelial APC/PAR1 distinctly regulates cytokine-induced pro-inflammatory VCAM-1 expression.Frontiers in molecular biosciences · 2023Article
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- Cellular crosstalk of glomerular endothelial cells and podocytes in diabetic kidney disease.Journal of cell communication and signaling · 2022Review
- Reversal of the renal hyperglycemic memory in diabetic kidney disease by targeting sustained tubular p21 expression.Nature communications · 2022Article
- Role of protease-activated receptor-1 (PAR-1) in the glomerular filtration barrier integrity.Physiological reports · 2022Article
- Glomerular cell cross talk in diabetic kidney diseases.Journal of diabetes · 2022Review
- Activated Protein C Ameliorates Tubular Mitochondrial Reactive Oxygen Species and Inflammation in Diabetic Kidney Disease.Nutrients · 2022Article
- Article
- Regulation of the Homeostatic Unfolded Protein Response in Diabetic Nephropathy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Gluten-Free Diet in Childhood Difficult-to-Treat Nephrotic Syndrome: A Pilot Feasibility Study.Glomerular diseases · 2022Article
- aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 8 institutions in 3 countries.
Funding
Abstract
The cytoprotective effects of activated protein C (aPC) are well established. In contrast, the receptors and signaling mechanism through which aPC conveys cytoprotection in various cell types remain incompletely defined. Thus, within the renal glomeruli, aPC preserves endothelial cells via a protease-activated receptor-1 (PAR-1) and endothelial protein C receptor-dependent mechanism. Conversely, the signaling mechanism through which aPC protects podocytes remains unknown. While exploring the latter, we identified a novel aPC/PAR-dependent cytoprotective signaling mechanism. In podocytes, aPC inhibits apoptosis through proteolytic activation of PAR-3 independent of endothelial protein C receptor. PAR-3 is not signaling competent itself as it requires aPC-induced heterodimerization with PAR-2 (human podocytes) or PAR-1 (mouse podocytes). This cytoprotective signaling mechanism depends on caveolin-1 dephosphorylation. In vivo aPC protects against lipopolysaccharide-induced podocyte injury and proteinuria. Genetic deletion of PAR-3 impairs the nephroprotective effect of aPC, demonstrating the crucial role of PAR-3 for aPC-dependent podocyte protection. This novel, aPC-mediated interaction of PARs demonstrates the plasticity and cell-specificity of cytoprotective aPC signaling. The evidence of specific, dynamic signaling complexes underlying aPC-mediated cytoprotection may allow the design of cell type specific targeted therapies.
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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.