Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Abstract
Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, and renal failure. We had proposed that a common set of transcriptional adaptations underlie the loss of muscle mass in these different states. To test this hypothesis, we used cDNA microarrays to compare the changes in content of specific mRNAs in muscles atrophying from different causes. We compared muscles from fasted mice, from rats with cancer cachexia, streptozotocin‐induced diabetes mellitus, uremia induced by subtotal nephrectomy, and from pair‐fed control rats. Although the content of >90% of mRNAs did not change, including those for the myofibrillar apparatus, we found a common set of genes (termed atrogins) that were induced or suppressed in muscles in these four catabolic states. Among the strongly induced genes were many involved in protein degradation, including polyubiquitins, Ub fusion proteins, the Ub ligases atrogin‐1/MAFbx and MuRF‐1, multiple but not all subunits of the 20S proteasome and its 19S regulator, and cathepsin L. Many genes required for ATP production and late steps in glycolysis were down‐regulated, as were many transcripts for extracellular matrix proteins. Some genes not previously implicated in muscle atrophy were dramatically up‐regulated (lipin, metallothionein, AMP deaminase, RNA helicase‐related protein, TG interacting factor) and several growth‐related mRNAs were down‐regulated (P311, JUN, IGF‐1‐BP5). Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases.—Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., Goldberg, A. L. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression.—Stewart H. Lecker, R. Thomas Jagoe, Alexander Gilbert, Marcelo Gomes, Vickie Baracos, James Bailey, S. Russ Price, William E. Mitch, Alfred L. Goldberg Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 18, 39–51 (2004)
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Genes encoding glycolysis and oxidative phosphorylation enzymes are coordinately suppressed in atrophying muscles during denervation, disuse, diabetes, cancer, fasting, and chronic kidney disease.
“Genes encoding for glycolysis and oxidative phosphorylation enzymes are coordinately suppressed in atrophying muscles during denervation, disuse, diabetes, cancer, fasting, and chronic kidney disease [10, 11, 13, 20].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [11]
Muscle atrophy requires activation of gene transcription programs that regulate expression of atrophy-related genes (atrogenes).
“Muscle atrophy requires the activation of gene transcription programs that regulate the expression of a subset of genes that are named atrophy-related genes or atrogenes [10–14].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [11]
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- Authors
- Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Aintree University Hospitals NHS Foundation Trust (GB)
- Harvard University (US)
- University of Alberta (CA)
- Emory University (US)
- The University of Texas Medical Branch at Galveston (US)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2004-01
- Volume
- 18
- Issue
- 1
- Pages
- 39-51
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2169448756
- Cited by
- 1,539
- References
- 89
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 41 · 2023: 62 · 2022: 49 · 2021: 70 · 2020: 51 · 2019: 70 · 2018: 73 · 2017: 66 · 2016: 77 · 2015: 76 · 2014: 86 · 2013: 91 · 2012: 111
- FWCI
- 28.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK02727)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- skeletal muscle atrophy, gene expression, protein degradation, ubiquitin ligase, atrogin-1/MAFbx, MuRF1, proteasome, cathepsin L, cancer cachexia, diabetes mellitus, uremia, starvation, transcriptional programs, extracellular matrix, lipin, metallothionein, AMP deaminase
- MeSH terms
- Adenosine Triphosphate, Animals, Gene Expression Regulation, Metallothionein, Muscular Atrophy, Nitrogen, Proteins, RNA, Messenger, Transcription Factors, Transcription, Genetic, Protein Biosynthesis, Extracellular Matrix Proteins, Muscle, Skeletal, Gene Expression Profiling, Ubiquitin-Protein Ligases, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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