Evidence map›Paper›PMID 36035360›Full record

ArticleJHEP reports : innovation in hepatology2022

Novel role of macrophage TXNIP-mediated CYLD-NRF2-OASL1 axis in stress-induced liver inflammation and cell death.

Yongqiang Zhan, Dongwei Xu, Yizhu Tian, Xiaoye Qu, Mingwei Sheng, Yuanbang Lin, Michael Ke, Longfeng Jiang, Qiang Xia, Fady M Kaldas and 2 more

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

Article in JHEP reports : innovation in hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
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  16. Ethyl Acetate Extract ofCurrent issues in molecular biology · 2025
    Article
  17. Article
  18. Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Yongqiang ZhanThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Dongwei XuThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Yizhu TianThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Xiaoye QuThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Mingwei ShengThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Yuanbang LinThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Michael KeThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Longfeng JiangThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Qiang XiaDepartment of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Fady M KaldasThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Douglas G FarmerThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Bibo KeThe Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
University of California, Los Angeles · USRenji Hospital · CN

Funding

Regulation of Innate Immune Responses by Alloimmunity in Liver Ischemia-Reperfusion InjuryP01AI120944 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Fady M Kaldas · 2017 to 2026
$20.0M
Innate Immune Regulation by HSF1 in Liver Inflammatory InjuryR01AI139552 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO · 2019 to 2023
$1.9M
CD47-SIRPalpha Signaling in Mesenchymal Stem Cell-Mediated Immune Regulation in Liver Transplant Inflammatory InjuryR21AI146742 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO · 2019 to 2020
$429k
Immune Regulation by Stem Cells: Role of Beta-Catenin in Liver Inflammatory InjuryR21AI115133 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO, KUPIEC-WEGLINSKI, JERZY W · 2017 to 2018
$428k
Beta-Catenin Signaling in Liver Ischemia and Reperfusion InjuryR21AI112722 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KE, BIBO, KUPIEC-WEGLINSKI, JERZY W · 2014 to 2015
$385k
NIAID NIH HHS P01 AI120944NIAID NIH HHS R01 AI139552NIAID NIH HHS R21 AI112722NIAID NIH HHS R21 AI115133NIAID NIH HHS R21 AI146742
6 · The paper itself

Abstract

Background & Aims: The stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) pathway is vital in mediating innate immune and inflammatory responses during oxidative/endoplasmic reticulum (ER) stress. However, it remains unknown whether macrophage thioredoxin-interacting protein (TXNIP) may regulate TBK1 function and cell death pathways during oxidative/ER stress. Methods: A mouse model of hepatic ischaemia/reperfusion injury (IRI), the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific TXNIP knockout (TXNIP Results: The TXNIP Conclusions: Macrophage TXNIP deficiency enhances CYLD activity and activates the NRF2-OASL1 signalling, controlling IR stress-induced liver injury. The target gene OASL1 regulated by NRF2 is crucial for modulating STING-mediated TBK1 activation and Apaf1/cytochrome c/caspase-9-triggered apoptotic/necroptotic cell death pathway. Our findings underscore a novel role of macrophage TXNIP-mediated CYLD-NRF2-OASL1 axis in stress-induced liver inflammation and cell death, implying the potential therapeutic targets in liver inflammatory diseases. Lay summary: Liver inflammation and injury induced by ischaemia and reperfusion (the absence of blood flow to the liver tissue followed by the resupply of blood) is a significant cause of hepatic dysfunction and failure following liver transplantation, resection, and haemorrhagic shock. Herein, we uncover an underlying mechanism that contributes to liver inflammation and cell death in this setting and could be a therapeutic target in stress-induced liver inflammatory injury.

Indexed as

ALT, alanine aminotransferaseAPAF1, apoptotic peptidase activating factor 1ApoptosisASK1, apoptosis signal-regulating kinase 1AST, aspartate aminotransferaseBMM, bone marrow-derived macrophageChIP, chromatin immunoprecipitationCXCL-10, C-X-C motif chemokine ligand 10CYLD, cyclindromatosisDAMP, damage-associated molecular patternDUB, deubiquitinating enzymeER, endoplasmic reticulumES, embryonic stemG3BP1G3BP1, Ras GTPase-activating protein-binding protein 1GCLC, glutamate-cysteine ligase catalytic subunitGCLM, glutamate-cysteine ligase regulatory subunitIHC, immunohistochemistryINF-β, interferon-βInnate immunityIRF3IRF3, interferon regulatory factor 3IRF7, IFN-regulating transcription factor 7IRI, ischaemia/reperfusion injuryIR, ischaemia/reperfusionKO, knockoutLiver inflammationLPS, lipopolysaccharideLyz2, Lysozyme 2MCP-1, monocyte chemoattractant protein 1NecroptosisNOX2, NADPH oxidase 2NOX4, NADPH oxidase 4NQO1, NAD(P)H quinone dehydrogenase 1NRF2, nuclear factor (erythroid-derived 2)-like 2NS, non-specificOASL1, 2′,5′oligoadenylate synthetase-like 1PAMP, pathogen-derived molecular patternRIPK3, receptor-interacting serine/threonine-protein kinase 3ROS, reactive oxygen speciessALT, serum ALTsAST, serum ASTsiRNA, small interfering RNASTINGSTING, stimulator of interferon genesTBK1, TANK-binding kinase 1TLR4, Toll-like receptor 4TNF-α, tumour necrosis factor-alphaTRX, thioredoxinTSS, transcription start sitesTXNIPFL/FL, floxed TXNIPTXNIPM-KO, myeloid-specific TXNIP KOTXNIP, thioredoxin-interacting proteinUTR, untranslated region

Identifiers

PMID36035360
PMCPMC9404660
OpenAlexW4284967369

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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.