Evidence map›Paper›PMID 39865408›Full record

ArticleJournal of cachexia, sarcopenia and muscle2025

Transcriptomic Profiling Reveals 17β-Estradiol Treatment Represses Ubiquitin-Proteasomal Mediators in Skeletal Muscle of Ovariectomized Mice.

Georgios Kararigas, Mara C Ebeling, Gengyun Le, Shaojuan Lai, Chunmei Cui, Qinghua Cui, Dawn A Lowe

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In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

7 authors.

Georgios KararigasDepartment of Physiology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Mara C EbelingDivision of Physical Therapy and Rehabilitation Science, Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.
Gengyun LeDivision of Physical Therapy and Rehabilitation Science, Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.
Shaojuan LaiDivision of Physical Therapy and Rehabilitation Science, Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.
Chunmei CuiDepartment of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, China.
Qinghua CuiDepartment of Biomedical Informatics, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, China.
Dawn A LoweDivision of Physical Therapy and Rehabilitation Science, Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0002-5784-9289

Funding

Interatction of Estrogen, Age and Activity on Musculoskeletal Strength in FemalesR01AG031743 · NIA · UNIVERSITY OF MINNESOTA · PI DAWN A LOWE · 2009 to 2026
$7.4M
Icelandic Cancer Society Research FundIcelandic Research Fund 217946-051NIA NIH HHS R01 AG031743NIH HHS R01AG031743University of Iceland Research Fund
6 · The paper itself

Abstract

backgroundWith a decline of 17β-estradiol (E2) at menopause, E2 has been implicated in the accompanied loss of skeletal muscle mass and strength. We aimed at characterizing transcriptomic responses of skeletal muscle to E2 in female mice, testing the hypothesis that genes and pathways related to contraction and maintenance of mass are differentially expressed in ovariectomized mice with and without E2 treatment.

methodsSoleus and tibialis anterior (TA) muscles from C57BL/6 ovariectomized mice treated with placebo (OVX) or E2 (OVX + E2) for 60 days, or from skeletal muscle-specific ERα knockout (skmERαKO) mice and wild-type littermates (skmERαWT), were used for genome-wide expression profiling, quantitative real-time PCR and immunoblotting. Computational detection of estrogen response elements (EREs) was performed with EREFINDER.

resultsWe found 155 significantly regulated probe sets in response to E2 (p ≤ 0.001). Pathway analyses identified proteasome and ubiquitin-mediated proteolysis as two downregulated pathways in the E2 group. We confirmed downregulation (p ≤ 0.05) in levels of Fbxw7, Psmb6, Ube2h and Ubxn1, as well as pro-apoptotic Bnip3 and inflammatory factor Nfkbia. Computational analysis identified ERE in the promoter regions of Psmb6, Ube2h, Bnip3 and Nfkbia. The overall content of ubiquitinated proteins was modestly but significantly lower in TA muscles from OVX + E2 vs. OVX mice (p = 0.039). There were no differences between skmERαKO and skmERαWT mice or between skmERαKO/OVX and skmERαKO/OVX + E2 mice for any genes assessed, indicating that ERα is required for E2 regulation of those genes.

conclusionsThese results suggest that a mechanism whereby E2 protects against losses of skeletal muscle mass and strength is regulation of ubiquitin-proteasomal mediators.

Indexed as

EstradiolGene Expression ProfilingMuscle, SkeletalProteasome Endopeptidase ComplexTranscriptomeUbiquitinAnimalsEstrogen Receptor alphaFemaleMiceMice, Inbred C57BLMice, KnockoutOvariectomyEstradiolEstrogen Receptor alphaProteasome Endopeptidase ComplexUbiquitinagingestrogenestrogen receptor αestrogen response element

Identifiers

PMID39865408
PMCPMC11761681

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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.