Evidence map›Paper›PMID 40801161›Full record

ArticleHuman molecular genetics2025

Transcriptome alterations underlying metabolic dysfunction and liver disease in myotonic dystrophy type 1.

Aono Fukumoto, Tomoki Yamanaka, Motoaki Yanaizu, Masayuki Nakamori, Manami Hama, Yoshiaki Yasumizu, Kana Shiotsu, Tsuyoshi Matsumura, Curtis A Nutter, Tomoya Kubota and 5 more

Abstract read
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In one paragraph

Article in Human molecular genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Aono FukumotoClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, The University of Osaka, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tomoki YamanakaClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, The University of Osaka, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Motoaki YanaizuDepartment of RNA Pathobiology and Therapeutics, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo 204-8588, Japan.
Masayuki NakamoriDepartment of Neurology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan.
Manami HamaClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, The University of Osaka, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yoshiaki YasumizuDepartment of Experimental Immunology, Immunology Frontier Research Center, The University of Osaka, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kana ShiotsuClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, The University of Osaka, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tsuyoshi MatsumuraDepartment of Neurology, NHO Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, Japan.
Curtis A NutterDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, 2033 Mowry Rd., Gainesville, FL 32610, United States.
Tomoya KubotaClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, The University of Osaka, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Harutoshi FujimuraDepartment of Neurology, NHO Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, Japan.
Yoshihiro KinoDepartment of RNA Pathobiology and Therapeutics, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo 204-8588, Japan.
Maurice S SwansonDepartment of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, College of Medicine, 2033 Mowry Rd., Gainesville, FL 32610, United States.ORCID 0000-0001-6245-5367
Kimiko InoueDepartment of Neurology, NHO Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka 560-8552, Japan.
Masanori P TakahashiClinical Neurophysiology, Department of Clinical Laboratory and Biomedical Sciences, Graduate School of Medicine, The University of Osaka, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan.ORCID 0000-0002-5513-5012

Funding

Training and Educational CoreU54NS048843 · NINDS · UNIVERSITY OF ROCHESTER · PI THORNTON, CHARLES A · 2003 to 2017
$21.9M
Senator Paul D. Wellstone Muscular Dystrophy Specialized Research CenterP50NS048843 · NINDS · UNIVERSITY OF ROCHESTER · PI THORNTON, CHARLES A · 2018 to 2022
$7.1M
Training and Educational CoreP50NS132955 · NINDS · UNIVERSITY OF FLORIDA · PI MAURICE SCOTT SWANSON · 2024 to 2026
$5.8M
Japan Agency for Medical Research and Development JP22ek0109474Japan Agency for Medical Research and Development JP25ek0109619Ministry of Education, Culture, Sports, Science, and Technology 22K07525Ministry of Health and Welfare of Japan 21FC1006Ministry of Health and Welfare of Japan 24FC1009National Center for Neurology and Psychiatry 5-5NIH HHS NS048843NIH HHS NS132955NINDS NIH HHS P50 NS048843NINDS NIH HHS P50 NS132955NINDS NIH HHS U54 NS048843
6 · The paper itself

Abstract

Myotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in the DMPK 3'-untranslated region, affecting multiple organs, including the skeletal muscles, eyes, heart, central nervous system, and endocrine system. A major pathogenic event in DM1 is the sequestration of muscleblind-like (MBNL) proteins by CUG repeat-containing RNAs transcribed from expanded repeats. Among the various symptoms of DM1, lipid abnormalities and liver dysfunction are frequent but remain understudied. Although abnormal splicing of insulin receptor RNA is implicated, it cannot fully explain these abnormalities. To investigate the molecular mechanisms, we performed transcriptome analysis of postmortem livers from patients with DM1 and Mbnl-knockout mice. RNA-sequencing revealed differentially expressed genes (DEGs) and aberrant splicing in DM1 livers. A comparison of Mbnl1- and Mbnl2-knockout mouse livers indicated that MBNL1 accounts for some of the transcriptomic changes observed in patients with DM1. The DEGs included those related to lipid metabolism and liver fibrosis. DM1-associated changes in the liver transcriptome partially resolved sexual dimorphism in gene expression and uncovered distinct sex-specific pathway alterations. Besides the known MBNL-regulated genes, those related to lipid and glucose metabolism were identified in the aberrant splicing clusters detected in DM1. A correlation between serum gamma-glutamyl transferase levels and overall splicing abnormalities was observed, linking splicing changes in the liver to clinical abnormalities. These findings provide new insights into the molecular basis of DM1-related metabolic and hepatic abnormalities, enhancing our understanding of the systemic effects of this disease.

Indexed as

Liver DiseasesMyotonic DystrophyTranscriptomeAnimalsDNA-Binding ProteinsFemaleGene Expression ProfilingHumansLipid MetabolismLiverMaleMiceMice, KnockoutMyotonin-Protein KinaseRNA-Binding ProteinsRNA SplicingDNA-Binding ProteinsMbnl1 protein, mouseMyotonin-Protein KinaseRNA-Binding ProteinsliverMBNLmousemRNAmyotonic dystrophy

Identifiers

PMID40801161
PMCPMC12498282

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.