High-resolution analysis of differential gene expression during skeletal muscle atrophy and programmed cell death
Authors
Tsuji, JunkoThomson, Travis
Chan, Elizabeth
Brown, Christine K.
Oppenheimer, Julia
Bigelow, Carol
Dong, Xianjun
Theurkauf, William E.
Weng, Zhiping
Schwartz, Lawrence M.
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Neurobiology
Program in Bioinformatics and Integrative Biology
Document Type
Journal ArticlePublication Date
2020-10-01Keywords
Manduca sextaautophagy
metamorphosis
proteasome
ubiquitin
Amino Acids, Peptides, and Proteins
Bioinformatics
Cell and Developmental Biology
Cellular and Molecular Physiology
Enzymes and Coenzymes
Genetics and Genomics
Molecular Biology
Nucleic Acids, Nucleotides, and Nucleosides
Metadata
Show full item recordAbstract
Skeletal muscles can undergo atrophy and/or programmed cell death (PCD) during development or in response to a wide range of insults, including immobility, cachexia, and spinal cord injury. However, the protracted nature of atrophy and the presence of multiple cell types within the tissue complicate molecular analyses. One model that does not suffer from these limitations is the intersegmental muscle (ISM) of the tobacco hawkmoth Manduca sexta. Three days before the adult eclosion (emergence) at the end of metamorphosis, the ISMs initiate a nonpathological program of atrophy that results in a 40% loss of mass. The ISMs then generate the eclosion behavior and initiate a nonapoptotic PCD during the next 30 h. We have performed a comprehensive transcriptomics analysis of all mRNAs and microRNAs throughout ISM development to better understand the molecular mechanisms that mediate atrophy and death. Atrophy involves enhanced protein catabolism and reduced expression of the genes involved in respiration, adhesion, and the contractile apparatus. In contrast, PCD involves the induction of numerous proteases, DNA methylases, membrane transporters, ribosomes, and anaerobic metabolism. These changes in gene expression are largely repressed when insects are injected with the insect steroid hormone 20-hydroxyecdysone, which delays death. The expression of the death-associated proteins may be greatly enhanced by reductions in specific microRNAs that function to repress translation. This study not only provides fundamental new insights into basic developmental processes, it may also represent a powerful resource for identifying potential diagnostic markers and molecular targets for therapeutic intervention.Source
Tsuji J, Thomson T, Chan E, Brown CK, Oppenheimer J, Bigelow C, Dong X, Theurkauf WE, Weng Z, Schwartz LM. High-resolution analysis of differential gene expression during skeletal muscle atrophy and programmed cell death. Physiol Genomics. 2020 Oct 1;52(10):492-511. doi: 10.1152/physiolgenomics.00047.2020. Epub 2020 Sep 14. PMID: 32926651. Link to article on publisher's site
DOI
10.1152/physiolgenomics.00047.2020Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29617PubMed ID
32926651Related Resources
ae974a485f413a2113503eed53cd6c53
10.1152/physiolgenomics.00047.2020