Cited by 1,539Muscle Physiology and DisordersNutrition and Health in AgingMuscle metabolism and nutrition

Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression

Lecker, Stewart H., Jagoe, R. Thomas, Gilbert, Alexander, Gomes, Marcelo, Baracos, Vickie, Bailey, James, Price, S. Russ, Mitch, William E. +1 more·2004·The FASEB Journal

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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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

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