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Skeletal muscle transcriptome is affected by age in severely burned mice
Juquan Song1, Steven G Widen2, Steven E Wolf1
1Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555-0644, USA. jusong@utmb.edu.
Insights
Severe burns significantly alter muscle gene expression differently in young versus adult mice. Age is a key factor influencing transcriptional responses to burn injury, impacting muscle health.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Severe burns cause muscle wasting, impacting patient quality of life.
- Distinct biological and metabolic profiles exist between pediatric and adult burn patients.
- Understanding age-related differences in muscle response to injury is crucial.
Purpose of the Study:
- To investigate age-dependent differences in muscle gene expression profiles following severe burn injury.
- To identify specific genes and pathways affected by burn injury in young versus adult mice.
Main Methods:
- Utilized Next Generation Sequencing (NGS) to analyze gene expression in gastrocnemius muscle.
- Compared gene expression patterns between young (5-week-old) and adult (11-week-old) C57BL6 male mice.
- Analyzed muscle tissue 24 hours post-scald burn or sham procedure.
Main Results:
- Significant differences in gene expression were observed between young and adult mice without injury (662 downregulated, 450 upregulated genes in young mice).
- Burn injury induced differential gene expression in both age groups compared to their respective controls.
- Key pathways affected by age included VEGFA-VEGFR2, focal adhesion, and nuclear receptors; proteasome degradation pathway showed similar changes in both age groups.
Conclusions:
- Severe burn injury elicits distinct muscle gene expression profiles in young and adult mice.
- Age significantly influences the transcriptional response to burn injury, affecting genes, microRNAs, pathways, and interactions.
- These findings highlight the importance of age in understanding burn-induced muscle wasting and recovery.
Abstract:
Severe burn results in muscle wasting affecting quality of life in both children and adults. Biologic metabolic profiles are noticeably distinctive in childhood. We posit that muscle gene expression profiles are differentially regulated in response to severe burns in young animals. Twelve C57BL6 male mice, including young (5 weeks-old) and adults (11 weeks-old), received either scald burn, or sham procedure. Mouse muscle tissue was harvested 24 h later for Next Generation Sequence analysis. Our results showed 662 downregulated and 450 upregulated genes in gastrocnemius of young mice compared to adults without injury. After injury, we found 74/75 downregulated genes and 107/128 upregulated genes in both burned groups compared to respective uninjured age groups. VEGFA-VEGFR2, focal adhesion, and nuclear receptor meta-pathways were the top 3 gene pathways undergoing a differential change in response to age. Of note, the proteasome degradation pathway showed the most similar changes in both adult and young burned animals. This study demonstrates the characteristic profile of gene expression in skeletal muscle in young and adult burned mice. Prominent age effects were revealed in transcriptional levels with increased alterations of genes, miRNAs, pathways, and interactions.
