Early regulation and alternative splicing dynamics in glucocorticoid muscle atrophy revealed by temporal omics in...

Area of Science:

• Biochemistry and Molecular Biology
• Cell Biology
• Physiology

Background:

• Skeletal muscle atrophy and weakness contribute significantly to disease morbidity, recovery time, and long-term disability.
• Understanding the molecular mechanisms of muscle atrophy is crucial for developing effective interventions.
• Complementarity of in vivo and in vitro models for studying muscle atrophy requires further exploration.

Purpose of the Study:

• To provide an updated view of dynamic changes during dexamethasone-induced atrophy using deep transcriptomic and proteomic profiling in the C2C12 murine skeletal muscle cell line.
• To assess the suitability of C2C12 cells as a model for studying early atrophy events and compare it with existing in vivo mouse data.
• To identify molecular alterations, including gene expression and alternative splicing, during early-stage myotube atrophy.

Main Methods:

• Deep coverage transcriptomic and proteomic profiling of C2C12 myotubes.
• Induction of skeletal muscle atrophy using dexamethasone.
• Comparison of C2C12 cell data with published in vivo mouse skeletal muscle data.
• Analysis of gene expression, particularly mitochondrial genes, and alternative splicing events.

Main Results:

• C2C12 myotubes effectively recapitulate muscle differentiation and atrophy markers, validating their use as an in vitro model.
• Dexamethasone treatment in C2C12 cells captured early molecular events characteristic of skeletal muscle atrophy.
• Identified significant alterations in mitochondrial gene expression and differential alternative splicing during early atrophy.
• The generated dataset complements existing in vivo data, offering a valuable resource for skeletal muscle atrophy research.

Conclusions:

• The C2C12 cell line is a suitable and valuable model for studying the molecular mechanisms of skeletal muscle atrophy, particularly early events.
• Deep molecular profiling reveals significant alternative splicing and mitochondrial gene expression changes during dexamethasone-induced atrophy.
• This study provides a comprehensive dataset that complements in vivo findings and enhances our understanding of skeletal muscle wasting.
• The findings offer novel insights into the regulatory processes underlying muscle atrophy, aiding future therapeutic strategies.