Evidence map›Paper›PMID 39803753›Full record

ArticleMolecular genetics & genomic medicine2025

Phenylbutyric Acid Modulates Apoptosis and ER Stress-Related Gene Expression in Glycogen Storage Disease Type Ib In Vitro Model.

Marina Parezanovic, Nina Stevanovic, Marina Andjelkovic, Milena Ugrin, Sonja Pavlovic, Maja Stojiljkovic, Anita Skakic

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In one paragraph

Article in Molecular genetics & genomic medicine, 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

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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.

Marina ParezanovicGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0003-2051-0529
Nina StevanovicGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0002-4215-3983
Marina AndjelkovicGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0002-4086-6197
Milena UgrinGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0002-7464-9406
Sonja PavlovicGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0002-2915-1641
Maja StojiljkovicGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0003-0625-2009
Anita SkakicGroup for Rare Disease Research and Therapeutics Development, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Republic of Serbia.ORCID https://orcid.org/0000-0002-1213-4458

Funding

Science Fund of the Republic of Serbia 6999
6 · The paper itself

Abstract

introductionChronic endoplasmic reticulum (ER) stress and increased apoptosis are involved in the pathogenesis of glycogen storage disease Ib (GSD Ib), whereas small molecule phenylbutyrate (4-PBA) showed the capability of reducing ER stress-induced apoptosis. The objective was to generate an in vitro system in which capability of small molecules (SMs) to influence ER stress and apoptosis could be screened at the expression level.

methodsG6PT-deficient FlpInHEK293 cell line was created and validated using the CRISPR/Cas9 knockout method. Molecular markers of unfolded protein response (ATF4, DDIT3, HSPA5, XBP1s), and apoptosis (BCL2/BAX, CASP3, CASP7) in G6PT-deficient cells were analyzed using RT-qPCR method before and upon the treatment with 4-PBA.

resultsTreatment with the most effective dose of 1 mM 4-PBA reduced the expression of UPR markers and executioner caspases, while increased BCL2/BAX ratio in G6PT-deficient cells. Our results proved the concept that 4-PBA could alleviate markers of ER stress detected in the GSD Ib in vitro model system and prevent cell death.

conclusionThis cost-effective in vitro model screens the therapeutic potential of SMs affecting ER stress and apoptosis in G6PT-deficient kidney cells, offering a first-line screening assay for promising compounds. 4-PBA's potential repurposing for GSD Ib patients opens new research directions.

Indexed as

ApoptosisEndoplasmic Reticulum StressGlycogen Storage Disease Type IPhenylbutyratesCell LineEndoplasmic Reticulum Chaperone BiPHumansUnfolded Protein Response4-phenylbutyric acidEndoplasmic Reticulum Chaperone BiPHSPA5 protein, humanPhenylbutyrates4‐PBAapoptosisCRISPR/Cas9ER stressGSD Ib in vitro model system

Identifiers

PMID39803753
PMCPMC11726116

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