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Published on: September 22, 2023
Identification of potential target genes associated with the reversion of androgen-dependent skeletal muscle atrophy
Priscila de O Coelho1, Flavia A Guarnier2, Leonardo Bruno Figueiredo3
1Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Abstract:
Muscle wasting or atrophy is extensively associated with human systemic diseases including diabetes, cancer, and kidney failure. Accumulating evidence from transcriptional profiles has noted that a common set of genes, termed atrogenes, is modulated in atrophying muscles. However, the transcriptional changes that trigger the reversion or attenuation of muscle atrophy have not been characterized at the molecular level until now. Here, we applied cDNA microarrays to investigate the transcriptional response of androgen-sensitive Levator ani muscle (LA) during atrophy reversion. Most of the differentially expressed genes behaved as atrogenes and responded to castration-induced atrophy. However, seven genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, and MKL1) did not respond to castration but instead responded exclusively to testosterone replacement. Considering that almost all proteins encoded by these genes are associated with the reversion of atrophy and may function as regulators of cell proliferation/growth, our results provide new perspectives on the existence of anti-atrogenes.
Insights
Researchers identified novel anti-atrogene genes that reverse muscle wasting. These genes exclusively respond to testosterone replacement, offering new insights into muscle atrophy attenuation.
Area of Science:
- Molecular Biology
- Physiology
- Genetics
Background:
- Muscle wasting (atrophy) is linked to systemic diseases like diabetes, cancer, and kidney failure.
- Atrogenes, a set of genes, are modulated during muscle atrophy.
- Molecular mechanisms driving muscle atrophy reversion remain largely uncharacterized.
Purpose of the Study:
- To investigate the transcriptional changes during muscle atrophy reversion.
- To identify genes specifically involved in reversing muscle wasting.
- To explore the role of testosterone in muscle regeneration at the molecular level.
Main Methods:
- Utilized cDNA microarrays to analyze gene expression in androgen-sensitive Levator ani muscle (LA).
- Compared gene expression profiles during castration-induced atrophy and testosterone replacement.
- Identified differentially expressed genes and their response patterns.
Main Results:
- Most differentially expressed genes acted as atrogenes, responding to castration.
- Identified seven specific genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, MKL1) that responded exclusively to testosterone replacement.
- Proteins encoded by these seven genes are linked to atrophy reversion and cell growth regulation.
Conclusions:
- Discovered a set of 'anti-atrogene' genes crucial for muscle atrophy reversal.
- These anti-atrogenes are regulated by testosterone, highlighting its role in muscle regeneration.
- Findings provide new molecular targets and perspectives for combating muscle wasting diseases.
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