Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
PLoS One. 2011 Feb 28;6(2):e17023. doi: 10.1371/journal.pone.0017023.
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-γ depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-γ 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-β 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.
施万细胞（SCs）是负责外周神经系统（PNS）髓鞘形成的细胞类型。由于视黄酸（RA）和其他类视黄醇对髓鞘形成程序有深远的影响，我们试图研究它们的核受体水平在这种细胞类型中是如何被调节的。
方法/主要发现：在本研究中，我们使用来自新生 Wistar 大鼠幼仔的施万细胞原代培养物，以及施万细胞与胚胎大鼠背根神经节感觉神经元的髓鞘共培养物，发现 RXR-γ 的持续表达依赖于不稳定激活剂的持续存在，而轴突接触模拟物则增加 RXR-γ mRNA 和蛋白水平，这种增加可以被 RA 阻止。轴突接触模拟物的上调和 RA 的转录下调依赖于新的蛋白质合成，不涉及 mRNA 稳定性的变化。另一方面，RAR-β mRNA 水平仅被轴突接触模拟物轻度调节，而 RA 产生的强烈转录上调不依赖于新的蛋白质合成，mRNA 稳定性没有变化。
结论/意义：综上所述，我们的结果表明，在外周神经系统中，视黄酸受体以复杂的方式被调节，这表明它们可能作为施万细胞生理学的调节剂发挥重要作用。
