PAR1 activation affects the neurotrophic properties of Schwann cells

Autor: Maria Eugenia Schininà, Virginia Correani, Bruno Maras, Lorenzo Fumagalli, Cinzia Fabrizi, Francesco Fornai, Francesca Somma, Marco Artico, Elena Pompili, Viviana Ciraci
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Protease-activated receptor-1
Nerve guidance conduit
Schwann cell
Ciliary neurotrophic factor
Protein Serine-Threonine Kinases
PC12 Cells
03 medical and health sciences
Cellular and Molecular Neuroscience
Myelin
0302 clinical medicine
medicine
Glial cell line-derived neurotrophic factor
Animals
Regeneration
Schwann cells
Nerve Growth Factors
Remyelination
Angiogenic Proteins
Rats
Wistar
Molecular Biology
Macrophage Migration-Inhibitory Factors
Cells
Cultured
biology
Complement C1r
Complement C1q
Cell Biology
Sciatic Nerve
Cell biology
Nerve Regeneration
Rats
Intramolecular Oxidoreductases
030104 developmental biology
medicine.anatomical_structure
nervous system
Peripheral nervous system
Culture Media
Conditioned
cardiovascular system
biology.protein
Female
Syndecan-4
Decorin
Neuroscience
030217 neurology & neurosurgery
Neurotrophin
Popis: 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.
Databáze: OpenAIRE
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