Evidence map›Paper›PMID 24779365›Full record

ArticleBMC research notes2014

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors.

Ortwin Naujok, Jana Lentes, Ulf Diekmann, Claudia Davenport, Sigurd Lenzen

Open access · goldAbstract read
In one paragraph

Article in BMC research notes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

69 citing papers in PubMed, 137 citations in OpenAlex.

  1. Article
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  9. Review
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  11. GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.Investigative ophthalmology & visual science · 2024
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  16. METTL3-dependent mCell death & disease · 2024
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  17. Review
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  19. Article
  20. Review

9 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Ortwin NaujokInstitute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str, 1, Hannover 30625, Germany. naujok.ortwin@mh-hannover.de.
Jana Lentes
Ulf Diekmann
Claudia Davenport
Sigurd Lenzen
Medizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSmall membrane-permeable molecules are now widely used during maintenance and differentiation of embryonic stem cells of different species. In particular the glycogen synthase kinase 3 (GSK3) is an interesting target, since its chemical inhibition activates the Wnt/beta-catenin pathway. In the present comparative study four GSK3 inhibitors were characterized.

methodsCytotoxicity and potential to activate the Wnt/beta-catenin pathway were tested using the commonly used GSK3 inhibitors BIO, SB-216763, CHIR-99021, and CHIR-98014. Wnt/beta-catenin-dependent target genes were measured by quantitative PCR to confirm the Wnt-reporter assay and finally EC50-values were calculated.

resultsCHIR-99021 and SB-216763 had the lowest toxicities in mouse embryonic stem cells and CHIR-98014 and BIO the highest toxicities. Only CHIR-99021 and CHIR-98014 lead to a strong induction of the Wnt/beta-catenin pathway, whereas BIO and SB-216763 showed a minor or no increase in activation of the Wnt/beta-catenin pathway over the natural ligand Wnt3a. The data from the Wnt-reporter assay were confirmed by gene expression analysis of the TCF/LEF regulated gene T.

conclusionsOut of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity.

Indexed as

AminopyridinesAnimalsBrachyury ProteinCell DeathCell DifferentiationCell LineCell SurvivalEmbryonic Stem CellsFetal ProteinsFluorescent Antibody TechniqueGene Expression RegulationGlycogen Synthase Kinase 3IndolesMaleimidesMiceOctamer Transcription Factor-3AminopyridinesBrachyury ProteinChir 98014Chir 99021Fetal ProteinsGlycogen Synthase Kinase 3IndolesMaleimidesOctamer Transcription Factor-3Pou5f1 protein, mouseProtein Kinase InhibitorsPyridinesPyrimidinesSB 216763T-Box Domain Proteins

Identifiers

PMID24779365
PMCPMC4008422
OpenAlexW2121372493

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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.