TY - JOUR A1 - Cencetti, Francesca A1 - Bruno, Gennaro A1 - Bernacchioni, Caterina A1 - Japtok, Lukasz A1 - Puliti, Elisa A1 - Donati, Chiara A1 - Bruni, Paola T1 - Sphingosine 1-phosphate lyase blockade elicits myogenic differentiation of murine myoblasts acting via Spns2/S1P(2) receptor axis JF - Biochimica et biophysica acta : Molecular and cell biology of lipids N2 - The bioactive sphingolipid sphingosine 1-phosphate (S1P) has emerged in the last three decades as main regulator of key cellular processes including cell proliferation, survival, migration and differentiation. A crucial role for this sphingolipid has been recognized in skeletal muscle cell biology both in vitro and in vivo. S1P lyase (SPL) is responsible for the irreversible degradation of S1P and together with sphingosine kinases, the S1P producing enzymes, regulates cellular S1P levels. In this study is clearly showed that the blockade of SPL by pharmacological or RNA interference approaches induces myogenic differentiation of C2C12 myoblasts. Moreover, down-regulation of the specific S1P transporter spinster homolog 2 (Spns2) abrogates myogenic differentiation brought about by SPL inhibition or down-regulation, pointing at a role of extracellular S1P in the pro-myogenic action induced by SPL blockade. Furthermore, also S1P(2) receptor down-regulation was found to abrogate the pro-myogenic effect of SPL blockade. These results provide further proof that inside-out S1P signaling is critically implicated in skeletal muscle biology and provide support to the concept that the specific targeting of SPL could represent an exploitable strategy to treat skeletal muscle disorders. KW - Sphingosine 1-phosphate KW - Myogenic differentiation Y1 - 2020 U6 - https://doi.org/10.1016/j.bbalip.2020.158759 SN - 1388-1981 SN - 1879-2618 VL - 1865 IS - 9 PB - Elsevier CY - Amsterdam ER -