Transcriptomic Profiling Reveals Differences in Slow-Twitch and Fast-Twitch Muscles of a Cigarette Smoke-Exposed Rat...

Area of Science:

• Muscle physiology
• Environmental toxicology
• Molecular biology

Background:

• Cigarette smoking (CS) impacts muscle function and exercise capacity, with known effects on slow-twitch muscles like the soleus.
• Limited research exists on CS effects on fast-twitch muscles and differential responses between muscle types.

Purpose of the Study:

• To investigate histomorphological, biochemical, and transcriptomic changes induced by CS in both slow-twitch (soleus) and fast-twitch (extensor digitorum longus - EDL) muscles.
• To elucidate the differential responses of muscle types to CS exposure.

Main Methods:

• Male Sprague-Dawley rats were exposed to CS or sham air (SA) for 8 weeks.
• Histomorphological analysis (fiber type, cross-sectional area), transcriptomic profiling (RNA sequencing), inflammatory marker assessment (macrophages, cytokines), and muscle proteolysis marker examination were performed on soleus and EDL muscles.

Main Results:

• Soleus muscle showed a significant increase in Type IIa fibers and a decrease in Type I fibers following CS exposure.
• RNA sequencing identified differentially expressed genes (DEGs) in soleus related to immune response and cellular signaling, with downregulated pathways linked to oxidative metabolism. EDL showed minimal changes.
• CS exposure elevated pro-inflammatory cytokines and macrophage markers (CD68) in soleus but not EDL. Atrogin-1 expression, a marker of muscle degradation, increased in soleus.

Conclusions:

• CS-induced inflammation in soleus muscle appears to target mitochondrial signaling, leading to dysfunction and reduced oxidative capacity.
• The less susceptible mitochondrial signaling in EDL muscle explains its differential response and resilience to CS exposure compared to soleus.