Evidence map›Paper›PMID 38329125›Full record

ArticleJCI insight2024

Cold stress-induced ferroptosis in liver sinusoidal endothelial cells determines liver transplant injury and outcomes.

Hidenobu Kojima, Hirofumi Hirao, Kentaro Kadono, Takahiro Ito, Siyuan Yao, Taylor Torgerson, Kenneth J Dery, Hiroaki Kitajima, Takahiro Ogawa, Fady M Kaldas and 2 more

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

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
14.3field-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

19 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
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  3. Article
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  11. Mouse orthotopic liver transplantation: Challenges, achievements, and applications.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Review
  12. Optimizing the mouse orthotopic liver transplantation model: Learning curve, technical enhancements, and keys to success.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2025
    Article
  13. Article
  14. 10 degree C static storage of porcine donation after circulatory death livers improves biliary viability and mitigates ischemia-reperfusion injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Article
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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 1 institution in 1 country.

Hidenobu KojimaDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Hirofumi HiraoDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kentaro KadonoDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Takahiro ItoDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Siyuan YaoDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Taylor TorgersonDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kenneth J DeryDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Hiroaki KitajimaWeintraub Center for Reconstructive Biotechnology, Division of Regenerative and Reconstructive Sciences, UCLA School of Dentistry, Los Angeles, California, USA.
Takahiro OgawaWeintraub Center for Reconstructive Biotechnology, Division of Regenerative and Reconstructive Sciences, UCLA School of Dentistry, Los Angeles, California, USA.
Fady M KaldasDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Douglas G FarmerDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jerzy W Kupiec-WeglinskiDumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
UCLA Health · US

Funding

Regulation of Innate Immune Responses by Alloimmunity in Liver Ischemia-Reperfusion InjuryP01AI120944 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ELAINE F REED · 2017 to 2026
$20.0M
NRF2 - SIRT1 SIGNALING AXIS IN LIVER TRANSPLANT REJUVENATIONR01DK062357 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2003 to 2025
$8.4M
THE RELAXIN RECEPTOR GR/RXFP1 SIGNALING IN LIVER TRANSPLANT ISCHEMIA-REPERFUSION INJURY AND THE INFLAMMATION RESOLUTIONR01AI155856 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2020 to 2024
$1.9M
Tim Costimulation in Liver Transplant Ischemia InjuryR01DK102110 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2015 to 2019
$1.7M
TIM-3 Negative Costimulation Signaling at the Innate-Adaptive Immune interface in Liver Transplant Ischemia-Reperfusion InjuryR01DK107533 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2016 to 2020
$1.7M
NIAID NIH HHS P01 AI120944NIAID NIH HHS R01 AI155856NIDDK NIH HHS R01 DK062357NIDDK NIH HHS R01 DK102110NIDDK NIH HHS R01 DK107533
6 · The paper itself

Abstract

Although cold preservation remains the gold standard in organ transplantation, cold stress-induced cellular injury is a significant problem in clinical orthotopic liver transplantation (OLT). Because a recent study showed that cold stress activates ferroptosis, a form of regulated cell death, we investigated whether and how ferroptosis determines OLT outcomes in mice and humans. Treatment with ferroptosis inhibitor (ferrostatin-1) during cold preservation reduced lipid peroxidation (malondialdehyde; MDA), primarily in liver sinusoidal endothelial cells (LSECs), and alleviated ischemia/reperfusion injury in mouse OLT. Similarly, ferrostatin-1 reduced cell death in cold-stressed LSEC cultures. LSECs deficient in nuclear factor erythroid 2-related factor 2 (NRF2), a critical regulator of ferroptosis, were susceptible to cold stress-induced cell death, concomitant with enhanced endoplasmic reticulum (ER) stress and expression of mitochondrial Ca2+ uptake regulator (MICU1). Indeed, supplementing MICU1 inhibitor reduced ER stress, MDA expression, and cell death in NRF2-deficient but not WT LSECs, suggesting NRF2 is a critical regulator of MICU1-mediated ferroptosis. Consistent with murine data, enhanced liver NRF2 expression reduced MDA levels, hepatocellular damage, and incidence of early allograft dysfunction in human OLT recipients. This translational study provides a clinically applicable strategy in which inhibition of ferroptosis during liver cold preservation mitigates OLT injury by protecting LSECs from peritransplant stress via an NRF2-regulatory mechanism.

Indexed as

CyclohexylaminesFerroptosisLiver TransplantationPhenylenediaminesAnimalsCalcium-Binding ProteinsCold-Shock ResponseEndothelial CellsHumansLiverMiceMitochondrial Membrane Transport ProteinsNF-E2-Related Factor 2Calcium-Binding ProteinsCyclohexylaminesferrostatin-1MICU1 protein, mouseMitochondrial Membrane Transport ProteinsNF-E2-Related Factor 2PhenylenediaminesApoptosis pathwaysImmunologyTransplantation

Identifiers

PMID38329125
PMCPMC10967411
OpenAlexW4394729438

What OpenQuestion holds

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LicenceCC BY
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.