ArticleProceedings of the National Academy of Sciences of the United States of America2018
TWEAK and RIPK1 mediate a second wave of cell death during AKI.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 143 citations in OpenAlex.
- A phase I, randomized, ascending-dose study to assess safety, pharmacokinetics, and activity of GDC-8264, a RIP1 inhibitor, in healthy volunteers.Clinical and translational science · 2023Trial
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- The RIPK3-IL-6 axis mediates kidney injury in cytokine storm syndrome.Cell death & disease · 2026Article
- Small molecules targeting regulated cell death for chronic kidney disease therapy.Journal of pharmaceutical analysis · 2026Review
- Cross-talk among novel programmed cell death pathways: a decisive network in renal ischemia-reperfusion injury.Frontiers in immunology · 2026Review
- A Five-Gene PANoptosis Signature Correlates with Immune Infiltration and Secondary Brain Injury in Intracerebral Hemorrhage.International journal of general medicine · 2026Article
- The TWEAK-HOIP-HuR Axis: A Novel Mechanism of AMPK Inactivation and Metabolic Reprogramming in Lupus Nephritis Mesangial Cells Hyperproliferation.Mediators of inflammation · 2026Article
- Remdesivir nephrotoxicity in tubular epithelial cells.Frontiers in pharmacology · 2026Article
- Nucleophosmin 1 lactylation in graft kidney induces ferroptotic trigger waves that exacerbate delayed graft function.Nature communications · 2025Article
- The role of ferroptosis in acute kidney injury: the preemptive mode of cell death and the bridging effect.Renal failure · 2025Review
- Discovery of Zharp1-163 as a dual inhibitor of ferroptosis and necroptosis for the treatment of inflammatory disorders and kidney injury.Cell death discovery · 2025Article
- Investigating the role of necroptosis in the immunological microenvironment of periodontitis.Molecular biology reports · 2025Article
- CCN2 Activates Cellular Senescence Leading to Kidney Fibrosis in Folic Acid-Induced Experimental Nephropathy.International journal of molecular sciences · 2025Article
- Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury.The Journal of clinical investigation · 2025Review
- Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice.iScience · 2025Article
- Curcuminoids as natural modulators of necroptosis: therapeutic implications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury.The Biochemical journal · 2025Article
- TWEAK-Fn14: a promising target for cardio-cerebrovascular diseases and brain-heart syndrome.Frontiers in immunology · 2025Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute kidney injury (AKI) is characterized by necrotic tubular cell death and inflammation. The TWEAK/Fn14 axis is a mediator of renal injury. Diverse pathways of regulated necrosis have recently been reported to contribute to AKI, but there are ongoing discussions on the timing or molecular regulators involved. We have now explored the cell death pathways induced by TWEAK/Fn14 activation and their relevance during AKI. In cultured tubular cells, the inflammatory cytokine TWEAK induces apoptosis in a proinflammatory environment. The default inhibitor of necroptosis [necrostatin-1 (Nec-1)] was protective, while caspase inhibition switched cell death to necroptosis. Additionally, folic acid-induced AKI in mice resulted in increased expression of Fn14 and necroptosis mediators, such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage domain-like protein (MLKL). Targeting necroptosis with Nec-1 or by genetic RIPK3 deficiency and genetic Fn14 ablation failed to be protective at early time points (48 h). However, a persistently high cell death rate and kidney dysfunction (72-96 h) were dependent on an intact TWEAK/Fn14 axis driving necroptosis. This was prevented by Nec-1, or MLKL, or RIPK3 deficiency and by Nec-1 stable (Nec-1s) administered before or after induction of AKI. These data suggest that initial kidney damage and cell death are amplified through recruitment of inflammation-dependent necroptosis, opening a therapeutic window to treat AKI once it is established. This may be relevant for clinical AKI, since using current diagnostic criteria, severe injury had already led to loss of renal function at diagnosis.
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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 OpenQuestion graph.