ArticleCell communication and signaling : CCS2024
Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting integrated cell death networks in sepsis‑associated acute kidney injury: Shared regulatory nodes and diet‑related small molecule modulation (Review).International journal of molecular medicine · 2026Review
- KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.International urology and nephrology · 2026Review
- Regulatory roles and translational potential of the Kruppel-like factor family in liver disease.iLIVER · 2026Review
- Programmed cell death in kidney disease: integrated crosstalk among ferroptosis, pyroptosis, apoptosis, and cuproptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH.Nature communications · 2026Article
- PARP7 alleviates lipopolysaccharide-induced acute kidney injury by inhibiting TBK1-driven inflammation in renal tubular epithelial cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- Acute kidney injury over the past decade: from definition evolution to pathogenesis insights and innovative therapeutic strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- Meta-analysis of functional genomics studies reveals conserved cellular pathways required by viruses of pandemic concern.Access microbiology · 2026Article
- NLRP3 inflammasome in acute kidney injury: molecular mechanisms, post-translational regulation, and immunotherapeutic potential.Frontiers in immunology · 2026Review
- Vitamin D/VDR Signaling and Programmed Cell Death in Sepsis-Associated Organ Injury: Evidence from Sepsis and Related Disease Models.Journal of inflammation research · 2026Review
- Dual Phosphorylation of STAT1 at Y701/S727 by TNFα Drives AIM2-Mediated PANoptosis of Renal Tubular Epithelial Cells and Fibrotic Progression in Renal Allografts.International journal of biological sciences · 2026Article
- Urinary acetylated protein as a biomarker of lupus nephritis: a prospective cohort study.Arthritis research & therapy · 2025Article
- Hydrogen Sulfide Attenuates Cisplatin-Induced Acute Kidney Injury via Dual Inhibition of Apoptosis and Pyroptosis.Biomedicines · 2025Article
- Research Progress on Signalling Pathways Related to Sepsis-Associated Acute Kidney Injury in Children.Current issues in molecular biology · 2025Review
- Magnetic engineered bone mesenchymal stem cells-derived exosomes for targeted acute lung injury therapy.Stem cell research & therapy · 2025Article
- Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis.Cellular & molecular biology letters · 2025Review
- Contribution of NLRP3-GSDMD axis to PDGF-BB-induced vascular smooth muscle cell phenotypic transition.American journal of physiology. Cell physiology · 2025Article
- Exploring lipid-modifying therapies for sepsis through the modulation of circulating inflammatory cytokines: a Mendelian randomization study.World journal of emergency medicine · 2025Article
- Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives.Critical care (London, England) · 2025Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPyroptosis of the renal tubular epithelial cells (RTECs) and interstitial inflammation are central pathological characteristics of acute kidney injury (AKI). Pyroptosis acts as a pro-inflammatory form of programmed cell death and is mainly dependent on activation of the NLRP3 inflammasome. Previous studies revealed that acetyl-CoA synthetase 2 (ACSS2) promotes inflammation during metabolic stress suggesting that ACSS2 might regulate pyroptosis and inflammatory responses of RTECs in AKI. METHODS AND
resultsThe expression of ACSS2 was found to be significantly increased in the renal epithelial cells of mice with lipopolysaccharide (LPS)-induced AKI. Pharmacological and genetic strategies demonstrated that ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the stimulation of the KLF5/NF-κB pathway in RTECs. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model, and ACSS2-deficient mice displayed impaired NLRP3 activation-mediated pyroptosis and decreased IL-1β production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and pyroptosis through the downregulation of the KLF5/NF-κB pathway. The KLF5 inhibitor ML264 suppressed NF-κB activity and NLRP3-mediated caspase-1 activation, thus protecting HK-2 cells from LPS-induced pyroptosis.
conclusionOur results suggested that ACSS2 regulates activation of the NLRP3 inflammasome and pyroptosis by inducing the KLF5/NF-κB pathway in RTECs. These results identified ACSS2 as a potential therapeutic target in AKI.
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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.