Evidence map›Paper›PMID 38936659›Full record

ArticleMolecular metabolism2024

Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.

Xiao Cheng, Vijaya Bhaskar Baki, Matthew Moran, Baolong Liu, Jiujiu Yu, Miaoyun Zhao, Qingsheng Li, Jean-Jack Riethoven, Channabasavaiah B Gurumurth, Edward N Harris and 1 more

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Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. A simple approach of nuclei isolation for single nucleus multiome sequencing.Journal of molecular and cellular cardiology · 2025
    Article
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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

11 authors.

Xiao ChengDepartment of Biochemistry, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA.
Vijaya Bhaskar BakiDepartment of Biochemistry, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA.
Matthew MoranDepartment of Biochemistry, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA.
Baolong LiuDepartment of Nutrition and Health Sciences, University of Nebraska - Lincoln, 230 Filley Hall, Lincoln, NE 68583-0922, USA.
Jiujiu YuDepartment of Nutrition and Health Sciences, University of Nebraska - Lincoln, 230 Filley Hall, Lincoln, NE 68583-0922, USA.
Miaoyun ZhaoNebraska Center for Virology, School of Biological Sciences, University of Nebraska - Lincoln, Lincoln, NE, USA.
Qingsheng LiNebraska Center for Virology, School of Biological Sciences, University of Nebraska - Lincoln, Lincoln, NE, USA.
Jean-Jack RiethovenNebraska Center for Biotechnology, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA; Nebraska Center for Integrated Biomolecular Communication (NCIBC), University of Nebraska - Lincoln, Lincoln, NE 68588, USA.
Channabasavaiah B GurumurthMouse Genome Engineering Core Facility, University of Nebraska Medical Center, Omaha, USA.
Edward N HarrisDepartment of Biochemistry, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA; Nebraska Center for Integrated Biomolecular Communication (NCIBC), University of Nebraska - Lincoln, Lincoln, NE 68588, USA; Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules, University of Nebraska - Lincoln, USA.
Xinghui SunDepartment of Biochemistry, University of Nebraska - Lincoln, Beadle Center, 1901 Vine St, Lincoln, NE 68588, USA; Nebraska Center for Integrated Biomolecular Communication (NCIBC), University of Nebraska - Lincoln, Lincoln, NE 68588, USA; Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules, University of Nebraska - Lincoln, USA. Electronic address: xsun17@unl.edu.

Funding

Role of lncRNA Meg3 in obesity-induced endothelial senescence and insulin resistanceR01HL150536 · NHLBI · UNIVERSITY OF NEBRASKA LINCOLN · PI SUN, XINGHUI · 2020 to 2023
$2.0M
Metabolism of Antisense Oligonucleotides and other Polyanions in LiverR01GM147913 · NIGMS · UNIVERSITY OF NEBRASKA LINCOLN · PI HARRIS, EDWARD N · 2022 to 2025
$1.3M
NHLBI NIH HHS R01 HL150536NIGMS NIH HHS R01 GM147913
6 · The paper itself

Abstract

objectiveThe prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise with the increasing obesity epidemic. Rezdiffra as an activator of a thyroid hormone receptor-beta is the only Food and Drug Administration approved therapy. As such, there is a critical need to improve our understanding of gene expression regulation and signaling transduction in MASLD to develop new therapies. Matrin-3 is a DNA- and RNA-binding protein involved in the pathogenesis of human diseases. Here we examined its previously uncharacterized role in limiting hepatic steatosis and stress response via the constitutive androstane receptor (CAR).

methodsMatrin-3 floxed and liver-specific knockout mice were fed either a chow diet or 60 kcal% high-fat diet (HFD) for up to 16 weeks. The mice were euthanized for different analysis including liver histology, lipid levels, and gene expression. Bulk RNA-seq, bulk ATAC-seq, and single-nucleus Multiome were used to examine changes of transcriptome and chromatin accessibility in the liver. Integrative bioinformatics analysis of our data and publicly available datasets and different biochemical assays were performed to identify underlying the molecular mechanisms mediating matrin-3's effects. Liver-tropic adeno-associated virus was used to restore the expression of CAR for lipid, acute phase genes, and histological analysis.

resultsMatrin-3 expression is induced in the steatotic livers of mice. Liver-specific matrin-3 deletion exacerbated HFD-induced steatosis, acute phase response, and inflammation in the liver of female mice. The transcriptome and chromatin accessibility were re-programmed in the liver of these mice with signatures indicating that CAR signaling is dysregulated. Mechanistically, matrin-3 interacts with CAR mRNA, and matrin-3 deficiency promotes CAR mRNA degradation. Consequently, matrin-3 deletion impaired CAR signaling by reducing CAR expression. Matrin-3 levels positively correlate with CAR expression in human livers. Ces2a and Il1r1 were identified as new target genes of CAR. Interestingly, we found that CAR discords with the expression of its target genes including Cyp2b10 and Ces2a in response to HFD, indicating CAR signaling is dysregulated by HFD despite increased CAR expression. Dysregulated CAR signaling upon matrin-3 deficiency reduced Ces2a and de-repressed Il1r1 expression. CAR restoration partially abrogated the dysregulated gene expression, exacerbated hepatic steatosis, acute phase response, and inflammation in liver-specific matrin-3 knockout mice fed a HFD.

conclusionsOur findings demonstrate that matrin-3 is a key upstream regulator maintaining CAR signaling upon metabolic stress, and the matrin-3-CAR axis limits hepatic steatosis and stress response signaling that may give insights for therapeutic intervention.

Indexed as

Constitutive Androstane ReceptorFatty LiverLiverMice, KnockoutAnimalsDiet, High-FatMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseNuclear Matrix-Associated ProteinsRNA-Binding ProteinsSignal TransductionStress, PhysiologicalConstitutive Androstane Receptormatrin-3 protein, mouseNuclear Matrix-Associated ProteinsRNA-Binding ProteinsConstitutive androstane receptorGene expressionMatrin-3SignalingSteatosisStress response

Identifiers

PMID38936659
PMCPMC11267048

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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.