Yang Hai Jie, Wang Lei, Wang Mian, Ma Shuang Ping, Cheng Bin Feng, Li Zhi Chao, Feng Zhi Wei
College of Life Science and Technology, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China.
J Mol Neurosci. 2015 Apr;55(4):977-84. doi: 10.1007/s12031-014-0454-9. Epub 2014 Oct 30.
Oligodendrocytes (OLs) are derived oligodendrocyte progenitor cells (OPCs), and their differentiation is a tightly regulated process. It is known that cyclin-dependent kinases (CDKs) play an essential role as regulators of OPC differentiation. Here, we newly identified a CDK-like protein, PFTK1, to be involved in OPC differentiation. With serum-deprivation, OLN-93 undergoes OL differentiation, and PFTK1 expression is markedly decreased during differentiation. When PFTK1 is silenced, OL differentiation is potentiated, as suggested by the increase of various differentiation markers CNPase, MOG, CGT, and MBP, by qPCR and Western blotting analysis. Vice versa, PTTK1 overexpression has opposite effects on OL differentiation of OLN-93 in vitro. Next, the modulation mechanism underlying OL differentiation of OLN-93 was investigated. Significantly, PFTK1 silencing leads to the activation of PI3K/AKT pathway, but no activation of MAPK/ERK pathway. The inhibition of AKT by its specific inhibitor abrogates PFTK1 silencing-promoted OL differentiation, indicating that PFTK1 negatively regulates OL differentiation through PI3K/AKT pathway. Together, these findings indicate a novel role played by PFTK1 in OL development, thus presenting opportunities to establish therapeutic approaches in improving neurological recovery related to demyelinating disorders.
少突胶质细胞（OLs）由少突胶质前体细胞（OPCs）分化而来，其分化过程受到严格调控。已知细胞周期蛋白依赖性激酶（CDKs）作为OPC分化的调节因子发挥着重要作用。在此，我们新鉴定出一种CDK样蛋白PFTK1参与OPC分化。血清剥夺时，OLN - 93细胞会发生OL分化，且分化过程中PFTK1表达明显降低。通过qPCR和蛋白质免疫印迹分析发现，当PFTK1沉默时，各种分化标志物如CNPase、MOG、CGT和MBP增加，提示OL分化增强。反之，PTTK1过表达对体外培养的OLN - 93细胞的OL分化有相反作用。接下来，研究了OLN - 93细胞OL分化的调控机制。值得注意的是，PFTK1沉默会导致PI3K/AKT通路激活，但不会激活MAPK/ERK通路。其特异性抑制剂抑制AKT可消除PFTK1沉默促进的OL分化，表明PFTK1通过PI3K/AKT通路负向调节OL分化。总之，这些发现表明PFTK1在OL发育中发挥了新作用，从而为建立改善脱髓鞘疾病相关神经恢复的治疗方法提供了机会。
