ArticleJournal of the American Society of Nephrology : JASN2015
Activated Protein C Ameliorates Renal Ischemia-Reperfusion Injury by Restricting Y-Box Binding Protein-1 Ubiquitination.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 83 citations in OpenAlex.
- Loss of Erbin in tubular epithelial cells sensitizes mice to acute kidney injury and aggravates renal fibrosis.The EMBO journal · 2026Article
- Ubiquitin-Conjugating Enzyme E2O Primes Hepatocytes to Restore Immune Tolerance in Autoimmune Hepatitis via Inhibiting Y-Box Binding Protein 1/Interleukin-6 Axis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Epigenetic and O-glycosylation regulation of p66Shc mitigates mitochondrial oxidative stress in aortic dissection.Theranostics · 2026Article
- Integrative Investigation of Flavonoids Targeting YBX1 Protein-Protein Interaction Network in Breast Cancer: From Computational Analysis to Experimental Validation.Molecular biotechnology · 2025Article
- OTUB1 antagonizes TRIM21 to induce deubiquitination of SPHK1 and promote the progression of hepatocellular carcinoma.Oncogene · 2025Article
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- Ubiquitin-specific protease 25 improves myocardial ischemia-reperfusion injury by deubiquitinating NLRP3 and negatively regulating NLRP3 inflammasome activity in cardiomyocytes.Clinical and translational medicine · 2025Article
- Characterizing Modulators of Protease-activated Receptors with a Calcium Mobilization Assay Using a Plate Reader.Journal of visualized experiments : JoVE · 2024Article
- Article
- A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway.Journal of translational medicine · 2024Article
- Review
- OTUB1-mediated inhibition of ubiquitination: a growing list of effectors, multiplex mechanisms, and versatile functions.Frontiers in molecular biosciences · 2023Review
- Partial otubain 1 deficiency compromises fetal well-being in allogeneic pregnancies despite no major changes in the dendritic cell and T cell compartment.BMC research notes · 2022Article
- Reversal of the renal hyperglycemic memory in diabetic kidney disease by targeting sustained tubular p21 expression.Nature communications · 2022Article
- EPCR-PAR1 biased signaling regulates perfusion recovery and neovascularization in peripheral ischemia.JCI insight · 2022Article
- OTUB1 augments hypoxia signaling via its non-canonical ubiquitination inhibition of HIF-1α during hypoxia adaptation.Cell death & disease · 2022Article
- ERK/RSK-mediated phosphorylation of Y-box binding protein-1 aggravates diabetic cardiomyopathy by suppressing its interaction with deubiquitinase OTUB1.The Journal of biological chemistry · 2022Article
- Article
- Aptamer loaded superparamagnetic beads for selective capturing and gentle release of activated protein C.Scientific reports · 2022Article
- YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy.Cells · 2022Review
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role of the coagulation system in renal IRI has been established, but the functional relevance of thrombomodulin (TM)-dependent activated protein C (aPC) generation and the intracellular targets of aPC remain undefined. Here, we investigated the role of TM-dependent aPC generation and therapeutic aPC application in a murine renal IRI model and in an in vitro hypoxia and reoxygenation (HR) model using proximal tubular cells. In renal IRI, endogenous aPC levels were reduced. Genetic or therapeutic reconstitution of aPC efficiently ameliorated renal IRI independently of its anticoagulant properties. In tubular cells, cytoprotective aPC signaling was mediated through protease activated receptor-1- and endothelial protein C receptor-dependent regulation of the cold-shock protein Y-box binding protein-1 (YB-1). The mature 50 kD form of YB-1 was required for the nephro- and cytoprotective effects of aPC in vivo and in vitro, respectively. Reduction of mature YB-1 and K48-linked ubiquitination of YB-1 was prevented by aPC after renal IRI or tubular HR injury. aPC preserved the interaction of YB-1 with the deubiquitinating enzyme otubain-1 and maintained expression of otubain-1, which was required to reduce K48-linked YB-1 ubiquitination and to stabilize the 50 kD form of YB-1 after renal IRI and tubular HR injury. These data link the cyto- and nephroprotective effects of aPC with the ubiquitin-proteasome system and identify YB-1 as a novel intracellular target of aPC. These insights may provide new impetus for translational efforts aiming to restrict renal IRI.
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