ABSTRACT
This review explores novel possibilities of skeletal muscle hypertrophy mechanism based on previous studies. Hypertrophy and/or regeneration of skeletal muscles are caused by activation of satellite cells, induced by mechanisms such as growth factors and cytokines. Many unsolved problems, however, yet remain concerning signaling pathways, activated by such substances, and regulation of transcriptional factors and cell cycles.In recent years, possible involvement of not only satellite cells but also tissue-specific stem cells in skeletal muscle hypertrophy has been reported from studies made on stem cell transplantation in muscle regeneration.It has been elucidated that differentiation plasticity of tissue-specific stem cells contributes to hypertrophy and/or regeneration of skeletal muscles. Moreover, satellite cells have come to be regarded as one kind of tissue-specific stem cells, since they have been known to exhibit diversity, by their differentiating into not only skeletal muscle cells but also other tissue cells, as well as self renewal capacity.This review also summarizes findings on signaling pathways based on ligand receptor characterization. Among the various signaling pathways, focus was especially placed on the possibilities of Wnt signaling pathway and Notch signaling pathway on skeletal muscle hypertrophy, indicating that Wnt expression in adult muscle stem cells leads to regulation of skeletal muscle hypertrophy.It has also become evident that Notch signaling pathway is associated with the activation of satellites cells, and that functional decline of such signaling pathway causes a decline in the activation of satellite cells. Such functional decline of Notch signaling pathway has also been revealed as the reason for the decline of regenerative capacity of skeletal muscles due to advancing age. Further discussion on the involvement of Notch signaling pathway in skeletal muscle hypertrophy is made based on these results. As indicated above, the roles of ligands and/or receptors of canonical growth factors, signaling pathways, and transcriptional factors contributing to skeletal muscle hypertrophy were reexamined in this review, after which the contribution of tissue-specific cells to skeletal muscle hypertrophy was discussed based on the results of muscle regeneration studies. Furthermore, focus was centered on Wnt and Notch signaling pathways, both of which are attracting renewed attention, and study was made on the possibility of the involvement of these pathways in skeletal muscle hypertrophy process.