Evidence map›Paper›PMID 37085901›Full record

ArticleCancer & metabolism2023

Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia.

Martijn G S Rutten, Yu Lei, Joanne H Hoogerland, Vincent W Bloks, Hong Yang, Trijnie Bos, Kishore A Krishnamurthy, Aycha Bleeker, Mirjam H Koster, Rachel E Thomas and 9 more

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

Article in Cancer & metabolism, 2023. 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
0.3field-weighted citation impact, top 31% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

19 authors at 6 institutions in 4 countries.

Martijn G S RuttenDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Yu LeiDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Joanne H HoogerlandDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Vincent W BloksDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hong YangScience for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.
Trijnie BosDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Kishore A KrishnamurthyDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Aycha BleekerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Mirjam H KosterDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Rachel E ThomasDepartment of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Justina C WoltersDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hilda van den BosEuropean Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Gilles MithieuxInstitut National de La Santé Et de La Recherche Médicale, U1213, Lyon, France.
Fabienne RajasInstitut National de La Santé Et de La Recherche Médicale, U1213, Lyon, France.
Adil MardinogluScience for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.
Diana C J SpieringsEuropean Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Alain de BruinDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Bart van de SluisDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Maaike H OosterveerDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. m.h.oosterveer@umcg.nl.
University of Groningen · NLUniversity Medical Center Groningen · NLKTH Royal Institute of Technology · SEInstitut National de Santé Publique · TNUniversité Claude Bernard Lyon 1 · FRUtrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia. As ChREBP has been proposed as a pro-oncogenic molecular switch that supports tumour progression, we hypothesized that ChREBP normalization protects against liver disease progression in hepatic GSD Ia.

methodsHepatocyte-specific G6pc knockout (L-G6pc

resultsHepatic ChREBP normalization in GSD Ia mice induced dysplastic liver growth, massively increased hepatocyte size, and was associated with increased hepatic inflammation. Furthermore, nuclear levels of the oncoprotein Yes Associated Protein (YAP) were increased and its transcriptional targets were induced in ChREBP-normalized GSD Ia mice. Hepatic ChREBP normalization furthermore induced DNA damage and mitotic activity in GSD Ia mice, while gene signatures of chromosomal instability, the cytosolic DNA-sensing cGAS-STING pathway, senescence, and hepatocyte dedifferentiation emerged.

conclusionsIn conclusion, our findings indicate that ChREBP activity limits hepatomegaly while decelerating liver disease progression and protecting against chromosomal instability in hepatic GSD Ia. These results disqualify ChREBP as a therapeutic target for treatment of liver disease in GSD Ia. In addition, they underline the importance of establishing the context-specific roles of hepatic ChREBP to define its therapeutic potential to prevent or treat advanced liver disease.

Indexed as

Carbohydrate Response Element Binding ProteinCyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING)Glycogen Storage Disease type 1aHepatomegalyYes Associated Protein

Identifiers

PMID37085901
PMCPMC10122297
OpenAlexW4366681300

What OpenQuestion holds

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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.