title: PAR1 activation affects the neurotrophic properties of Schwann cells.
abstract: Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR.
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy. Electronic address: elena.pompili@uniroma1.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Pompili
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fabrizi
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Somma
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Correani
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Maras
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ciraci
authors.affiliation: Department of Sensory Organs, Sapienza University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Artico
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy; IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fumagalli
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D015922:Complement C1q / Q000235:genetics / Q000378:metabolism; D015923:Complement C1r / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D058575:Decorin / Q000235:genetics / Q000378:metabolism; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism
chemical_list: C000620722:AGGF1 protein, rat; D042501:Angiogenic Proteins; D017077:Culture Media, Conditioned; C546880:Dcn protein, rat; D058575:Decorin; D008263:Macrophage Migration-Inhibitory Factors; D009414:Nerve Growth Factors; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D015922:Complement C1q; C000623348:F2r protein, rat; D017346:Protein Serine-Threonine Kinases; D015923:Complement C1r; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat
keywords: Peripheral nervous system; Protease-activated receptor-1; Regeneration; Schwann cells