title: Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression.
abstract: S1P lyase (SPL) catalyzes the irreversible degradation of sphingosine-1-phosphate (S1P), a bioactive lipid whose signaling activities regulate muscle differentiation, homeostasis, and satellite cell (SC) activation. By regulating S1P levels, SPL also controls SC recruitment and muscle regeneration, representing a potential therapeutic target for muscular dystrophy. We found that SPL is induced during myoblast differentiation. To investigate SPL's role in myogenesis at the cellular level, we generated and characterized a murine myoblast SPL-knockdown (SPL-KD) cell line lacking SPL. SPL-KD cells accumulated intracellular and extracellular S1P and failed to form myotubes under conditions that normally stimulate myogenic differentiation. Under differentiation conditions, SPL-KD cells also demonstrated delayed induction of 3 myogenic microRNAs (miRNAs), miR-1, miR-206, and miR-486. SPL-KD cells successfully differentiated when treated with an S1P1 agonist, S1P2 antagonist, and combination treatments, which also increased myogenic miRNA levels. SPL-KD cells transfected with mimics for miR-1 or miR-206 also overcame the differentiation block. Thus, we show for the first time that the S1P/SPL/S1P-receptor axis regulates the expression of a number of miRNAs, thereby contributing to myogenic differentiation.
authors.affiliation: 1Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA. jsaba@chori.org.
authors.forename: Anabel S
authors.initials: AS
authors.lastname: de la Garza-Rodea
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Baldwin
authors.forename: Babak
authors.initials: B
authors.lastname: Oskouian
authors.forename: Robert F
authors.initials: RF
authors.lastname: Place
authors.forename: Padmavathi
authors.initials: P
authors.lastname: Bandhuvula
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Julie D
authors.initials: JD
authors.lastname: Saba
mesh_terms: D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D035683:MicroRNAs; D049349:Receptors, Lysosphingolipid; C572630:Spns2 protein, mouse; D000446:Aldehyde-Lyases; C022649:sphingosine 1-phosphate lyase (aldolase)
keywords: C2C12; Spns2; myogenesis; sphingolipid