Evidence map›Paper›PMID 29937272›Full record

ArticleCell host & microbe2018

Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis.

Rui Kang, Ling Zeng, Shan Zhu, Yangchun Xie, Jiao Liu, Qirong Wen, Lizhi Cao, Min Xie, Qitao Ran, Guido Kroemer and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell host & microbe, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 388 papers.

0numbers the graph read from it
0cells of the map it votes in
388citing papers in PubMed
15.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

388 citing papers in PubMed, 584 citations in OpenAlex.

  1. Article
  2. Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Mechanistic insights into ferroptosis in thyroid cancer and its therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Oxeiptosis - potential in cancer treatment?Expert reviews in molecular medicine · 2026
    Review
  20. Article

328 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 11 institutions in 4 countries.

Rui KangThe Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Protein Modification and Degradation Laboratory of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510510, China; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Ling ZengState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Research Institute for Traffic Medicine of People's Liberation Army, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Shan ZhuThe Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Protein Modification and Degradation Laboratory of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
Yangchun XieDepartment of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Jiao LiuThe Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Protein Modification and Degradation Laboratory of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
Qirong WenThe Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Protein Modification and Degradation Laboratory of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
Lizhi CaoDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Min XieDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Qitao RanDepartment of Cell Systems and Anatomy, University of Texas Health Science Center, Research Service, South Texas Veterans Health Care System, San Antonio, TX 78229, USA.
Guido KroemerUniversité Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France; Equipe 11 Labellisée Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Institut National de La Santé et de La Recherche Médicale, U1138 Paris, France; Université Pierre et Marie Curie, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France; Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden.
Haichao WangLaboratory of Emergency Medicine, North Shore University Hospital, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
Timothy R BilliarDepartment of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Jianxin JiangState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Research Institute for Traffic Medicine of People's Liberation Army, Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: jiangjx@cta.cq.cn.
Daolin TangThe Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Protein Modification and Degradation Laboratory of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510510, China; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: tangd2@upmc.edu.
Third Affiliated Hospital of Guangzhou Medical University · CNGuangzhou Medical University · CNArmy Medical University · CNCentral South University · CNDaping Hospital · CNFeinstein Institute for Medical Research · USSecond Xiangya Hospital of Central South University · CNSouth Texas Veterans Health Care System · USUniversité Paris Cité · FRUniversity of Pittsburgh · USXiangya Hospital Central South University · CN

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
Regulation and Function of Endotoxin Signaling in Surgical SepsisR01GM050441 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BILLIAR, TIMOTHY R · 1994 to 2018
$4.6M
Mechanisms of Novel Herbal Therapies for Sepsis.R01AT005076 · NCCIH · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI WANG, HAICHAO · 2010 to 2023
$4.3M
Regulation of HMGB1 Release in Endotoxemia.R01GM063075 · NIGMS · NORTH SHORE UNIVERSITY HOSPITAL · PI WANG, HAICHAO · 2002 to 2020
$4.2M
Targeting HMGB1-mediated Autophagy in Cancer TherapyR01CA160417 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI TANG, DAOLIN · 2012 to 2023
$3.0M
NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMAR01GM044100 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BILLIAR, TIMOTHY R · 1995 to 2017
$1.9M
Immunometabolism in SepsisR01GM115366 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI BILLIAR, TIMOTHY R, TANG, DAOLIN · 2015 to 2018
$1.2M
EPA EP-C-16-014NCCIH NIH HHS R01 AT005076NCI NIH HHS P30 CA047904NCI NIH HHS R01 CA160417NIGMS NIH HHS R01 GM044100NIGMS NIH HHS R01 GM050441NIGMS NIH HHS R01 GM063075NIGMS NIH HHS R01 GM115366
6 · The paper itself

Abstract

Sepsis is a life-threatening condition caused by pathogen infection and associated with pyroptosis. Pyroptosis occurs upon activation of proinflammatory caspases and their subsequent cleavage of gasdermin D (GSDMD), resulting in GSDMD N-terminal fragments that form membrane pores to induce cell lysis. Here, we show that antioxidant defense enzyme glutathione peroxidase 4 (GPX4) and its ability to decrease lipid peroxidation, negatively regulate macrophage pyroptosis, and septic lethality in mice. Conditional Gpx4 knockout in myeloid lineage cells increases lipid peroxidation-dependent caspase-11 activation and GSDMD cleavage. The resultant N-terminal GSDMD fragments then trigger macrophage pyroptotic cell death in a phospholipase C gamma 1 (PLCG1)-dependent fashion. Administration of the antioxidant vitamin E that reduces lipid peroxidation, chemical inhibition of PLCG1, or genetic Caspase-11 deletion or Gsdmd inactivation prevents polymicrobial sepsis in Gpx4

Indexed as

AnimalsApoptosis Regulatory ProteinsCaspasesCaspases, InitiatorCoinfectionDisease Models, AnimalEscherichia coliGasderminsGlutathione PeroxidaseHeLa CellsHL-60 CellsHumansIntracellular Signaling Peptides and ProteinsLeukocytes, MononuclearLipid PeroxidationMacrophagesApoptosis Regulatory ProteinsCasp4 protein, mouseCaspasesCaspases, InitiatorGasderminsGlutathione Peroxidaseglutathione peroxidase 4, mouseGsdmd protein, mouseIntracellular Signaling Peptides and ProteinsPhosphate-Binding ProteinsPhospholipid Hydroperoxide Glutathione PeroxidaseVitamin Ecaspase-11ferroptosisGPX4GSDMDimmunometabolisminflammasomelipid peroxidationpyroptosissepsis

Identifiers

PMID29937272
PMCPMC6043361
OpenAlexW2808965517

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.