Burn injury dysregulates protein signaling in type 1 and type 2 muscles in rats

Skeletal muscle wasting is one of the systemic hallmarks of severe burn injuries. The underlying mechanisms of muscle wasting post-burn, and in particular the differences between muscle fiber types, are not well understood. This study aimed to investigate the protein signaling pathways involved in skeletal muscle atrophy following severe burn injury.

11 rats were submitted to sham injury and 11 rats to a severe burn (40% total body surface area burn) using the Walker-Mason burn model. Muscle samples from predominantly type II m. extensor digitorum longus (EDL) and predominantly type I m. soleus (SOL) were collected 40 days post-burn. Body and muscle weights, immunohistochemistry and Western blotting were used to assess anthropometric differences and the expression of key proteins involved in protein imbalance causing muscle wasting.

Rats with severe burn injury showed less body weight gain (39.73 ± 10.97 g vs 77.12 ± 4.83 g; p < 0.01) and lower muscle wet weights of both SOL (123.1 ± 3.63 mg vs 102.7 ± 3.67 mg; p < 0.001) and EDL (127.9 ± 2.95 mg vs 110.3 ± 2.80 mg; p < 0.001) compared to sham-treated rats. Immunohistochemical analysis revealed no significant differences in fiber type distribution between the groups. Western blot analysis showed altered expression of proteins involved in protein synthesis and proteolysis pathways, with differences between SOL and EDL muscles. In SOL, severe burns induce inhibition of anabolic pAkt (p < 0.0001) and eEF2 signaling (p < 0.05), while in EDL increased levels of pAkt (p < 0.01) were found. Catabolic E3 ligases MURF1,2,3 and Atrogin-1 show higher activation in SOL after severe burn injury (p < 0.0001; both) but not in EDL, where decreases were found (p < 0.0001; p < 0.001; respectively). Analysis of myokines post-burn in SOL show lower expression of Decorin (p < 0.0001) and higher of myostatin (p < 0.0001), but in EDL both myostatin and irisin expressions were lower (p < 0.001; p < 0.05; respectively).

Severe burn injury resulted in skeletal muscle wasting, as evidenced by decreased body weight gain in growing rats and reduced muscle weights. Protein signaling pathways related to protein synthesis and proteolysis are dysregulated in muscles of burned rats, with significant differences between slow- and fast-twitch muscles. Further research is needed to understand the long-term effects of postburn metabolism on skeletal muscle protein balance and develop targeted therapies to prevent muscle wasting in burn survivors.