Key result
Upregulation of Fbxo32 and Trim63 mRNA was associated with reduced muscle fiber cross-sectional area and skeletal muscle atrophy in mice (ES -3.89; 95% CI -4.45 to -3.32).
Why the study?
Muscle atrophy causes weakness and mortality, and while E3 ubiquitin ligases play a critical role in atrophic mechanisms, the association between specific atrogene mRNA levels and muscle cross-sectional area reductions needed evaluation.
Does the upregulation of Fbxo32 and Trim63 mRNA correlate with skeletal muscle atrophy in murine models?
Meta-Analysis (n=29)
Does the upregulation of Fbxo32 and Trim63 mRNA correlate with skeletal muscle atrophy in murine models?
Standardized Mean Difference: -3.89 (95% CI -4.45–-3.32)
The magnitude of increase in muscle Fbxo32 and Trim63 mRNA is a feasible and reliable molecular marker for skeletal muscle atrophy in mice.
MAFbx/MuRF1 mRNA upregulation reliably marks atrophy; supports biomarker use in preclinical models while leaving clinical translation open.
Muscle atrophy leads to decreased muscle mass, weakness, inactivity, and increased mortality. E3 ubiquitin ligases, key regulators of protein degradation via the ubiquitin–proteasome system, play a critical role in atrophic mechanisms. This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and its objective was to evaluate the association between E3 ligases Muscle Atrophy F-box (MAFbx)/Atrogin-1 (Fbxo32) and Muscle RING-finger protein 1 (MuRF-1) (TRIM63) E3 ligase mRNA levels, reductions in skeletal muscle CSA measures, and atrophy conditions. We examined papers published on PubMed®, Scopus, and Web of Science that studied E3 ligase gene expression signatures for Fbxo32 (MAFbx/Atrogin-1) and Trim63 (MuRF1) in different types of muscle atrophy and hypertrophy murine models. Twenty-nine studies selected by two independent raters were analyzed. Standardized mean differences (SMDs)/effect sizes (ESs) and 95% confidence intervals (CIs) were calculated for the outcomes using fixed-effects models. We found that 6- and 4.8-fold upregulation, respectively, of Fbxo32 and Trim63 was sufficient to reduce the ES to −3.89 (95% CI: −4.45 to −3.32) for the muscle fiber cross-sectional area and the development of skeletal muscle atrophy. I² and Q test statistics did not indicate heterogeneous data. There was a low probability of bias after both the funnel plot and Egger’s test analyses. These results were sustained independently of the atrophic model and muscle type. Therefore, the magnitude of the increase in muscle Fbxo32 and Trim63 mRNA is a feasible, reliable molecular marker for skeletal muscle atrophy in mice. The next step for the Ubiquitin-proteasome system (UPS) field involves elucidating the targets of E3 ligases, paving the way for diagnostic and treatment applications in humans.
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Gouvêa et al. (2025) conducted a meta-analysis in Skeletal muscle atrophy (n=29). Fbxo32 and Trim63 mRNA upregulation was evaluated on Muscle fiber cross-sectional area and development of skeletal muscle atrophy (ES -3.89, 95% CI -4.45 to -3.32). Upregulation of Fbxo32 and Trim63 mRNA was associated with reduced muscle fiber cross-sectional area and skeletal muscle atrophy in mice (ES -3.89; 95% CI -4.45 to -3.32).
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