Role of sphingosine 1-phosphate metabolism and signalling in skeletal muscle atrophy and fibrosis

In the last 30 years, multiple roles of S1P have been demonstrated in the regulation of skeletal muscle biology. The presented study is focused on the role of S1P metabolism in myogenic differentiation, where SPL was found playing a crucial role in regulating S1P cellular levels and responsible for onset of myogenic program. The role of S1P axis was also confirmed in skeletal muscle atrophy induced by TNF-alpha. S1P signalling pathwayplays a crucial role in the development and maintenance of the fibrotic process. New S1P3 antagonists were tested to antagonise the receptor involved in fibrosis, and new SK inhibitors have been designed on the base of PF-543, with the aim to develop glycohybrids as potential pharmacological tool in skeletal muscle fibrosis. The metabolism of S1P appears a promising drug targets for pharmacological therapies in skeletal muscle repair.