Thyroid hormone signaling in skeletal muscle regeneration

Skeletal muscle has a high capability to regenerate after injury mostly because of the presence of muscle stem cells (MuSCs). In certain situations, such as severe injuries (accidents, combat, and surgical injuries) or degenerative diseases (muscle dystrophies), skeletal muscle loss cannot be repaired. This could be an even more burden for the VA healthcare because combat Veterans have a higher risk of deployment-related muscle injuries and long-term disabilities. Thyroid hormones act as pleiotropic factors in various tissues during development by regulating genes involved in growth and differentiation, including skeletal muscle. Thyroid hormones and thyroid hormone receptor α (THRA) play a crucial role in MuSCs proliferation and differentiation and skeletal muscle regeneration after injury. This proposal will test the role of thyroid hormone signaling on MuSC function during skeletal muscle regeneration in response to injury. We are planning several studies devoted to extending our knowledge on the molecular basis of thyroid hormone signaling in skeletal muscle regeneration after injury. We will further explore the collaborative interaction between THRA and COUP-TFII and their role in skeletal muscle regeneration with in vitro and in vivo models. We plan to use new in vitro system and in vivo mouse models that will allow studies on muscle regeneration. Our goal is to identify therapeutic targets with the potential to promote MuSC proliferation and differentiation in response to injury that can be useful for skeletal muscle repair and myopathies.