Department of Orthopaedic Surgery, University of California, Irvine, Irvine, CA, United States.
Neurosci Lett. 2009 Nov 13;465(2):194-8. doi: 10.1016/j.neulet.2009.09.014. Epub 2009 Sep 16.
Limited work has been done to investigate the molecular mechanisms behind the process of demyelination and remyelination that occurs in response to chronic nerve compression (CNC) injury. In the present study, we investigated the expression of the transcription factors krox-20 and c-jun, positive and negative regulators of myelination, respectively. A decrease in krox-20 expression and an increase in c-jun expression in both its phosphorylated and non-phosphorylated states were observed. In addition, we investigated the role of integrins, specifically the beta4 subunit of the alpha6beta4 dimer, as a possible upstream signal transducer in the signaling cascade leading to demyelination. We detected a decrease in beta4 integrin expression at 2 and 4 weeks post-injury and a concomitant relocalization to the Schmidt-Lanterman Incisures, suggesting a role for the beta4 integrin in facilitating Schwann cell-extracellular matrix interaction. The observed changes in transcription factor and integrin expression are temporally correlated with the process of demyelination, and suggest further investigation to define their definitive role in regulating the myelin response to CNC injury.
针对慢性神经压迫(CNC)损伤后发生的脱髓鞘和髓鞘再生过程的分子机制,目前的研究工作还很有限。在本研究中,我们研究了转录因子 krox-20 和 c-jun 的表达情况,它们分别是髓鞘形成的正、负调节因子。我们观察到,krox-20 的表达减少,其磷酸化和非磷酸化状态的 c-jun 表达增加。此外,我们还研究了整合素(integrin)的作用,特别是 alpha6beta4 二聚体的 beta4 亚基,作为导致脱髓鞘的信号级联反应中的一个可能的上游信号转导物。我们在损伤后 2 周和 4 周时检测到 beta4 整合素表达减少,并伴有 Schmidt-Lanterman 切迹的重新定位,这表明 beta4 整合素在促进施旺细胞-细胞外基质相互作用中起作用。转录因子和整合素表达的观察到的变化与脱髓鞘过程在时间上相关,这表明需要进一步研究以确定它们在调节 CNC 损伤后髓鞘反应中的明确作用。