Evidence map›Paper›PMID 40550888›Full record

ArticleCellular and molecular life sciences : CMLS2025

The metabolic shift of glutaminase 2 to glutaminase 1 promotes LGR5 + progenitor cell proliferation in liver cirrhosis.

Defu Kong, Qi Zhou, Kang He, Janette Heegsma, Hans Blokzijl, Vincent E de Meijer, Klaas Nico Faber

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

7 authors.

Defu KongDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. defu.kong@outlook.com.ORCID http://orcid.org/0000-0003-2448-7792
Qi ZhouDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands.
Kang HeDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Janette HeegsmaDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands.
Hans BlokzijlDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands.
Vincent E de MeijerDepartment of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Klaas Nico FaberDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. k.n.faber@umcg.nl.

Funding

China Scholarship Council 201906230336
6 · The paper itself

Abstract

BACKGROUND AND

aimLiver regeneration is impaired in end-stage liver disease characterized by advanced fibrosis and cirrhosis, where metabolic reprogramming is considered as a therapeutic target. The shift in glutaminolysis from liver-type Glutaminase 2 (GLS2) to kidney-type Glutaminase 1 (GLS1) is crucial in different liver diseases, though its role in liver progenitor cell-mediated regeneration remains unclear. This study aimed to analyze the expression of glutamine-metabolizing enzymes in fibrotic human livers and investigate the role of GLS1 in LGR5

methodsHealthy and chronically diseased human liver tissue from patients with alcoholic liver disease, viral hepatitis, biliary atresia, primary biliary cholangitis or non-alcoholic steatohepatitis were immunostained for GLS1, GLS2 and glutamine synthetase (GS), and co-stained for LGR5. GLS1 was inhibited in adult progenitor cell-rived human liver organoids to evaluate its role in stemness and cell proliferation pathways.

resultsGLS1 expression was enhanced and GLS2 decreased in chronic liver diseases compared to healthy liver. GLS1 was expressed in parenchymal, including hepatocytes, and non-parenchymal cells. In cirrhotic livers, GLS1

conclusionsThis study identifies GLS1 as a metabolic regulator of progenitor cell expansion aiding liver regeneration in various etiologies of human liver cirrhosis.

Indexed as

GlutaminaseLiver CirrhosisReceptors, G-Protein-CoupledStem CellsCell ProliferationFemaleHumansLiverLiver RegenerationMaleOrganoidsProtein Glutamine gamma Glutamyltransferase 2GLS2 protein, humanGLS protein, humanGlutaminaseLGR5 protein, humanProtein Glutamine gamma Glutamyltransferase 2Receptors, G-Protein-CoupledGlutaminase 1Glutamine metabolismGSHLiver fibrosisLiver organoidsProliferation

Identifiers

PMID40550888
PMCPMC12185844

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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.