title: S100B protein regulates myoblast proliferation and differentiation by activating FGFR1 in a bFGF-dependent manner.
abstract: S100B protein has been shown to exert anti-myogenic and mitogenic effects in myoblast cultures through inhibition of the myogenic p38 MAPK and activation of the mitogenic ERK1/2. However, the receptor mediating these effects had not been identified. Here, we show that S100B increases and/or stabilizes the binding of basic fibroblast growth factor (bFGF) to bFGF receptor 1 (FGFR1) by interacting with bFGF, thereby enhancing FGFR1 activation and the mitogenic and anti-myogenic effects of FGFR1. S100B also binds to its canonical receptor RAGE (receptor for advanced glycation end-products), a multi-ligand receptor previously shown to transduce a pro-myogenic signal when activated by HMGB1, and recruits RAGE into a RAGE-S100B-bFGF-FGFR1 complex. However, when bound to S100B-bFGF-FGFR1, RAGE can no longer stimulate myogenic differentiation, whereas in the absence of either bFGF or FGFR1, binding of S100B to RAGE results in stimulation of RAGE anti-mitogenic and promyogenic signaling. An S100B-bFGF-FGFR1 complex also forms in Rage(-/-) myoblasts, leading to enhanced proliferation and reduced differentiation, which points to a dispensability of RAGE for the inhibitory effects of S100B on myoblasts under the present experimental conditions. These results reveal a new S100B-interacting protein - bFGF - in the extracellular milieu and suggest that S100B stimulates myoblast proliferation and inhibits myogenic differentiation by activating FGFR1 in a bFGF-dependent manner.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences and Istituto Interuniversitario di Miologia, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Riuzzi
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Sorci
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D010766:Phosphorylation; D000067759:Receptor for Advanced Glycation End Products; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D009414:Nerve Growth Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1