The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release of IL-6. Transient release and short-term acute action have positive effects, by increasing the source of progenitors for regeneration and growth in skeletal muscle. This also affects metabolic processes in other organs, since it stimulates glucose production. In different circumstances, chronically elevated levels of IL-6 have negative consequences, promoting muscle atrophy through different mechanisms not completely yet elucidated. These antithetical effects can also be a key to the several discrepancies observed with different experimental approaches aimed to decipher the IL-6/JAK/STAT role in skeletal muscle functions. Moreover, the different cell and tissue compartments where IL-6 is produced and acts can account for the conflicting effects observed on muscle repair, growth, and wasting. Additionally, a role in these dichotomous outcomes can also be car...
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