ArticleKidney international2023
Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.
Article in Kidney international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Nanomaterial-Based Precision Drug Delivery for Advanced Nephrology Therapy: A Systematic Review.International journal of nanomedicine · 2026Pooled it
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Vascular Non-Inflammatory Molecule-1 Aggravates Acute Kidney Injury Induced Acute Lung Injury Via Promoting Neutrophil Extracellular Traps Formation.Inflammation · 2026Article
- Plant metabolites: potential treatments for ischemic acute kidney injury.Frontiers in pharmacology · 2026Review
- Salidroside protects against high-altitude hypoxia-induced kidney injury via regulation of renal dopamine D1-like receptors.PloS one · 2026Article
- Prediction model and significance of myocardial injury induced by fluorouracil combined with platinum-based chemotherapy in advanced gastric cancer based on baseline data and inflammation-nutrition-atherosclerosis factors.Frontiers in medicine · 2025Article
- 5-methoxytryptophan ameliorates renal ischemia/reperfusion injury by alleviating endoplasmic reticulum stress-mediated apoptosis through the Nrf2/HO-1 pathway.Frontiers in pharmacology · 2025Article
- Type I collagen-targeted liposome delivery of Serca2a modulates myocardium calcium homeostasis and reduces cardiac fibrosis induced by myocardial infarction.Materials today. Bio · 2024Article
- The roles of G protein-coupled receptor kinase 2 in renal diseases.Journal of cellular and molecular medicine · 2024Review
- Mitochondria-Associated Organelle Crosstalk in Myocardial Ischemia/Reperfusion Injury.Journal of cardiovascular translational research · 2024Review
- G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- [High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
Ischemia/reperfusion injury of the kidney is associated with high morbidity and mortality, and treatment of this injury remains a challenge. G protein-coupled receptor kinase 4 (GRK4) plays a vital role in essential hypertension and myocardial infarction, but its function in kidney ischemia/reperfusion injury remains undetermined. Among the GRK subtypes (GRK2-6) expressed in kidneys, the increase in GRK4 expression was much more apparent than that of the other four GRKs 24 hours after injury and was found to accumulate in the nuclei of injured mouse and human renal tubule cells. Gain- and loss-of-function experiments revealed that GRK4 overexpression exacerbated acute kidney ischemia/reperfusion injury, whereas kidney tubule-specific knockout of GRK4 decreased injury-induced kidney dysfunction. Necroptosis was the major type of tubule cell death mediated by GRK4, because GRK4 significantly increased receptor interacting kinase (RIPK)1 expression and phosphorylation, subsequently leading to RIPK3 and mixed lineage kinase domain-like protein (MLKL) phosphorylation after kidney ischemia/reperfusion injury, but was reversed by necrostatin-1 pretreatment (an RIPK1 inhibitor). Using co-immunoprecipitation, mass spectrometry, and siRNA screening studies, we identified signal transducer and activator of transcription (STAT)1 as a GRK4 binding protein, which co-localized with GRK4 in the nuclei of renal tubule cells. Additionally, GRK4 phosphorylated STAT1 at serine 727, whose inactive mutation effectively reversed GRK4-mediated RIPK1 activation and tubule cell death. Kidney-targeted GRK4 silencing with nanoparticle delivery considerably ameliorated kidney ischemia/reperfusion injury. Thus, our findings reveal that GRK4 triggers necroptosis and aggravates kidney ischemia/reperfusion injury, and its downregulation may provide a promising therapeutic strategy for kidney protection.
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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 Socratic graph.