Evidence map›Paper›PMID 38727301›Full record

ArticleCells2024

Novel Inositol 1,4,5-Trisphosphate Receptor Inhibitor Antagonizes Hepatic Stellate Cell Activation: A Potential Drug to Treat Liver Fibrosis.

Natalia Smith-Cortinez, Janette Heegsma, Masa Podunavac, Armen Zakarian, J César Cardenas, Klaas Nico Faber

Abstract read
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

6 authors.

Natalia Smith-CortinezDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
Janette HeegsmaDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
Masa PodunavacDepartment of Chemistry and Biochemistry, University of California, Oakland, CA 94607, USA.
Armen ZakarianDepartment of Chemistry and Biochemistry, University of California, Oakland, CA 94607, USA.
J César CardenasDepartment of Chemistry and Biochemistry, University of California, Oakland, CA 94607, USA.ORCID 0000-0003-1115-2790
Klaas Nico FaberDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Liver fibrosis, characterized by excessive extracellular matrix (ECM) deposition, can progress to cirrhosis and increases the risk of liver cancer. Hepatic stellate cells (HSCs) play a pivotal role in fibrosis progression, transitioning from a quiescent to activated state upon liver injury, wherein they proliferate, migrate, and produce ECM. Calcium signaling, involving the inositol 1,4,5-trisphosphate receptor (IP3R), regulates HSC activation. This study investigated the efficacy of a novel IP3R inhibitor, desmethylxestospongin B (dmXeB), in preventing HSC activation. Freshly isolated rat HSCs were activated in vitro in the presence of varying dmXeB concentrations. The dmXeB effectively inhibited HSC proliferation, migration, and expression of fibrosis markers without toxicity to the primary rat hepatocytes or human liver organoids. Furthermore, dmXeB preserved the quiescent phenotype of HSCs marked by retained vitamin A storage. Mechanistically, dmXeB suppressed mitochondrial respiration in activated HSCs while enhancing glycolytic activity. Notably, methyl pyruvate, dimethyl α-ketoglutarate, and nucleoside supplementation all individually restored HSC proliferation despite dmXeB treatment. Overall, dmXeB demonstrates promising anti-fibrotic effects by inhibiting HSC activation via IP3R antagonism without adverse effects on other liver cells. These findings highlight dmXeB as a potential therapeutic agent for liver fibrosis treatment, offering a targeted approach to mitigate liver fibrosis progression and its associated complications.

Indexed as

Cell ProliferationHepatic Stellate CellsInositol 1,4,5-Trisphosphate ReceptorsLiver CirrhosisAnimalsCell MovementHumansRatsInositol 1,4,5-Trisphosphate Receptorscalciumhepatic stellate cellsliver fibrosismitochondrial metabolism

Identifiers

PMID38727301
PMCPMC11083487

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.