Injury to the recurrent laryngeal nerve often leads to permanent
vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term
denervation can induce laryngeal muscle
fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of
fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of
fibrosis-related factors, including transforming growth factor-β1 (TGF-β1),
connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of
accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for
denervation experiments. Masson's trichrome staining showed that the grade of
atrophy and
fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after
denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after
denervation (p < 0.05) and was maintained at its high level until 4 weeks. CTGF- and α-SMA-positive muscle cells were detected at 1 week after
denervation, peaked at 2 weeks (p < 0.05), and remained at high levels with a subsequent slight decrease for 3-4 weeks. These results suggest that TGF-β1 and CTGF may be involved in the process of denervated skeletal muscle
fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key
pathological processes in denervated skeletal muscle
fibrosis and develop novel therapeutic strategies.