Evidence map›Paper›PMID 36422999›Full record

ArticleJCI insight2023

Gsk3β regulates the resolution of liver ischemia/reperfusion injury via MerTK.

Hanwen Zhang, Ming Ni, Han Wang, Jing Zhang, Dan Jin, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Wei Li, Xuehao Wang, Yuan Zhai

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. 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
1.9field-weighted citation impact, top 14% 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, 23 citations in OpenAlex.

  1. Article
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  6. Beyond a Biomarker: Investigations of a Proinflammatory Role for Cell-Free DNA in Liver Transplant Ischemia and Reperfusion.Transplant international : official journal of the European Society for Organ Transplantation · 2026
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  8. Review
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  16. Efferocytosis in liver disease.JHEP reports : innovation in hepatology · 2024
    Review
  17. Article
  18. Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2023
    Review
  19. 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

10 authors at 5 institutions in 1 country.

Hanwen ZhangDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Ming NiDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Han WangDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Jing ZhangDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Dan JinDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Ronald W BusuttilDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Jerzy W Kupiec-WeglinskiDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Wei LiDepartment of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Xuehao WangHepatobiliary Center, Key Laboratory of Liver Transplantation of Chinese Academy of Medical Sciences, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yuan ZhaiDumont-UCLA Transplant Center, Department of Surgery, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Nanjing Medical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNJilin University · CNRenji Hospital · CNUnion 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
Proteomics CoreP30DK123704 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DON C. ROCKEY · 2020 to 2026
$8.8M
Glycogen Synthase Kinase 3 beta in liver ischemia reperfusion injuryR01DK119338 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHAI, YUAN · 2020 to 2023
$1.4M
NIAID NIH HHS P01 AI120944NIDDK NIH HHS P30 DK123704NIDDK NIH HHS R01 DK119338
6 · The paper itself

Abstract

Although glycogen synthase kinase β (Gsk3β) has been shown to regulate tissue inflammation, whether and how it regulates inflammation resolution versus inflammation activation is unclear. In a murine liver, partial warm ischemia/reperfusion injury (IRI) model, we found that Gsk3β inhibitory phosphorylation increased at both the early-activation and late-resolution stages of the disease. Myeloid Gsk3β deficiency not only alleviated liver injuries, it also facilitated the restoration of liver homeostasis. Depletion of Kupffer cells prior to the onset of liver ischemia diminished the differences between the WT and Gsk3β-KO mice in the activation of liver IRI. However, the resolution of liver IRI remained accelerated in Gsk3β-KO mice. In CD11b-DTR mice, Gsk3β-deficient BM-derived macrophages (BMMs) facilitated the resolution of liver IRI as compared with WT cells. Furthermore, Gsk3β deficiency promoted the reparative phenotype differentiation in vivo in liver-infiltrating macrophages and in vitro in BMMs. Gsk3 pharmacological inhibition promoted the resolution of liver IRI in WT, but not myeloid MerTK-deficient, mice. Thus, Gsk3β regulates liver IRI at both activation and resolution stages of the disease. Gsk3 inactivation enhances the proresolving function of liver-infiltrating macrophages in an MerTK-dependent manner.

Indexed as

Glycogen Synthase Kinase 3Reperfusion InjuryAnimalsc-Mer Tyrosine KinaseGlycogen Synthase Kinase 3 betaInflammationIschemiaLiverMicec-Mer Tyrosine KinaseGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseMertk protein, mouseHepatologyImmunologyInnate immunityMacrophages

Identifiers

PMID36422999
PMCPMC9870084
OpenAlexW4309912986

What OpenQuestion holds

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LicenceCC BY
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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.