Ricerc@Sapienza

Thyroid hormones regulate a wide range of cellular responses, via non-genomic and genomic actions, depending on cell-specific thyroid hormone transporters, co-repressors, or co-activators. Skeletal muscle has been identified as a direct target of thyroid hormone T3, where it regulates stem cell proliferation and differentiation, as well as myofiber metabolism. However, the effects of T3 in muscle-wasting conditions have not been yet addressed.

Muscle stem cells, or satellite cells, are a population of adult stem cells involved in muscle growth and indispensable for adult skeletal muscle regeneration. As the quiescent state is perturbed, satellite cells undergo profound metabolic changes, named metabolic reprogramming, driving cellular activation, commitment and differentiation. Thus, modulation of cellular metabolism, by altered nutrient availability or with aging, can impact satellite cell stemness and fate, as well as differentiation ability.

Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. These events favor tumor progression and chemoresistance.