title: Sphingosine 1-phosphate signaling axis mediates fibroblast growth factor 2-induced proliferation and survival of murine auditory neuroblasts.
abstract: Hearing loss affects millions of people in the world. In mammals the auditory system comprises diverse cell types which are terminally differentiated and with no regenerative potential. There is a tremendous research interest aimed at identifying cell therapy based solutions or pharmacological approaches that could be applied therapeutically alongside auditory devices to prevent hair cell and neuron loss. Sphingosine 1-phosphate (S1P) is a pleiotropic bioactive sphingolipid that plays key role in the regulation of many physiological and pathological functions. S1P is intracellularly produced by sphingosine kinase (SK) 1 and SK2 and exerts many of its action consequently to its ligation to S1P specific receptors (S1PR), S1P1-5. In this study, murine auditory neuroblasts named US/VOT-N33 have been used as progenitors of neurons of the spiral ganglion. We demonstrated that the fibroblast growth factor 2 (FGF2)-induced proliferative action was dependent on SK1, SK2 as well as S1P1and S1P2. Moreover, the pro-survival effect of FGF2 from apoptotic cell death induced by staurosporine treatment was dependent on SK but not on S1PR. Additionally, ERK1/2 and Akt signaling pathways were found to mediate the mitogenic and survival action of FGF2, respectively. Taken together, these findings demonstrate a crucial role for S1P signaling axis in the proliferation and the survival of otic vesicle neuroprogenitors, highlighting the identification of possible novel therapeutical approaches to prevent neuronal degeneration during hearing loss.
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bruno
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy.
authors.forename: Ilaria Maria
authors.initials: IM
authors.lastname: Rizzo
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Romero-Guevara
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bernacchioni
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cencetti
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy. Electronic address: chiara.donati@unifi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Donati
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche "M. Serio", viale G B Morgagni 50, 50134 Firenze, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bruni
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D016222:Fibroblast Growth Factor 2; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Auditory neuroblasts; Fibroblast growth factor 2; Proliferation; Sphingosine 1-phosphate; Sphingosine 1-phosphate receptor; Survival