Regulation of retinoid receptors by retinoic acid and axonal contact in Schwann cells

[Background]: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear recepto...

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Detalles Bibliográficos
Autores: Latasa, María Jesús, Cosgaya, José Miguel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/39731
Acceso en línea:http://hdl.handle.net/10261/39731
Access Level:acceso abierto
Palabra clave:Peripheral nervous-system
X-receptor
In-vitro
Gene-expression
Growth-factor
Stem-cells
Rar-beta-2 promoter
Human neuroblastoma
Stromal cells
Neural crest
Descripción
Sumario:[Background]: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type. [Methodology/Principal Findings]: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-gamma depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-gamma mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-beta mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without changes in mRNA stability. [Conclusions/Significance]: All together, our results show that retinoid receptors are regulated in a complex manner in Schwann cells, suggesting that they could have a prominent role as regulators of Schwann cell physiology.