Effects of Ghrelin peptides on skeletal and cardiac muscle regeneration

The thesis is divided in two parts. Part I describes effects of unacyated ghrelin, a small peptide mainly produced by stomach with multiple biological effects, on muscle regeneration in dystrophic condition using the murine mdx model. This study shows that unacylated ghrelin stimulates the polarity complex-mediated assymetric division of satellite cells, stem cells of muscle, leading to increase regenerative potential of satellite cells that in turn leads to the reduction of muscle degeneration and overall improvement of muscle function. These data were published in "Unacylated ghrelin enhances satellite cell function and relieves the dystrophic phenotype in Duchenne muscular dystrophy mdx model" (Reano et al., 2017, Stem cells) and a detailed protocol describing satellite cell handling in "Mouse satellite cell isolation and transplantaion" (Angelino et al., 2018, Bio-protocol). Moreover, Part I contains a study of the effect of unacylated ghrelin on cardiac muscle in mdx mice willing to establish if unacylated ghrelin treatment improved cardiac function in dystrophic mice. To complete information about the endogenous role of ghrelin peptides in muscle regeneration, Ghrl-/- mice, which lack all ghrelin gene products, have been investigated resulting in "Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal" (Angelino et al., Endocrine, under revision). Part II describes the in vitro study of the effect of vitamin D metabolites 25(OH)D and 1,25(OH)2D on skeletal muscle, both in normal condition and upon cytokine-induced cachexia, showing that these two metabolites have opposite effects: in basal condition, 25(OH)D induces hypertrophy while 1,25(OH)2D causes atrophy, and upon cytokine-induced atrophy, only 25(OH)D has a protective effect.