ArticleCell death and differentiation2020
RIPK3 collaborates with GSDMD to drive tissue injury in lethal polymicrobial sepsis.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Macrophages in Renal Injury, Repair, Fibrosis Following Acute Kidney Injury and Targeted Therapy.Frontiers in immunology · 2022Pooled it
- Review
- Mapping the holonomic signaling network that drives pathological changes in endotoxic shock.Cellular & molecular immunology · 2026Article
- Co-exposure to Cadmium and Polystyrene Nanoplastics Intensifies Renal Damage in Mice via the Activation of the PANoptosis Pathway.Biological trace element research · 2026Article
- Dual targeting of NCF1 and NLRP3 by roburic acid orchestrates redox homeostasis and inhibits macrophage death in septic lung injury.Redox biology · 2026Article
- The RIPK3-IL-6 axis mediates kidney injury in cytokine storm syndrome.Cell death & disease · 2026Article
- Specific features of the infection caused by SARS-CoV-2 variants in Vero cell culture.Archives of virology · 2026Article
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Cell death mechanisms in heat stroke and sepsis: ZBP1 and caspase-11 as molecular sensors driving the MLKL/GSDMD death execution axis.Frontiers in cell and developmental biology · 2026Review
- 1-Nitropyrene induces acute lung injury via SYVN1/Caspase-11-mediated apoptosis and pyroptosis in pulmonary epithelial cells.Frontiers in pharmacology · 2026Article
- Crosstalk of regulated cell death pathways in sepsis-associated acute kidney injury: implications for therapy.Frontiers in cell and developmental biology · 2026Review
- Interleukin-39 aggravates sepsis by inducing self-sustaining neutrophil activation in the lungs via the CXCL1-CXCR2 pathway.International journal of biological sciences · 2026Article
- Caspases and programmed cell death in sepsis: mechanisms, pathophysiology, and therapeutic targets.Frontiers in immunology · 2026Review
- Research progress on the role of mesenchymal stem cells in pyroptosis in sepsis.Stem cell research & therapy · 2025Review
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Delaying pyroptosis with an AI-screened gasdermin D pore blocker mitigates inflammatory response.Nature immunology · 2025Article
- Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis.Cellular & molecular biology letters · 2025Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis is a systemic inflammatory disease causing life-threatening multi-organ dysfunction. Accumulating evidences suggest that two forms of programmed necrosis, necroptosis and pyroptosis triggered by the pathogen component lipopolysaccharide (LPS) and inflammatory cytokines, play important roles in the development of bacterial sepsis-induced shock and tissue injury. Sepsis-induced shock and tissue injury required receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) phosphorylation, caspase11 activation and gasdermin D (GSDMD) cleavage. However, the synergistic effect of necroptosis and pyroptosis in the pathological progress of sepsis remains elusive. In this study, we found that blockage of both necroptosis and pyroptosis (double deletion of Ripk3/Gsdmd or Mlkl/Gsdmd) resulted in accumulative protection against septic shock, systemic blood clotting and multi-organ injury in mice. Bone marrow transplantation confirmed that necroptosis and pyroptosis in both myeloid and nonmyeloid cells are indispensable in the progression of sepsis-induced multi-organ injury. Both RIPK3 and GSDMD signaling collaborated to amplify necroinflammation and tissue factor release in macrophages and endothelial cells, which led to tissue injury. Furthermore, cell death induced by inflammatory cytokines and high-mobility group box 1 could be prevented by double ablation of Ripk3/Gsdmd or Mlkl/Gsdmd, suggesting that a positive feedback loop interconnecting RIPK3/MLKL and GSDMD machinery and inflammation facilitated sepsis progression. Collectively, our findings demonstrated that RIPK3-mediated necroptosis and GSDMD-mediated pyroptosis collaborated to amply inflammatory signaling and enhance tissue injury in the process of sepsis, which may shed new light on two potential targets of combined therapeutic interventions for this highly lethal disorder.
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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.