A novel role of cyclin-dependent kinase PFTK1 in the differentiation of oligodendrocyte precursor cells

Yang Hai-jie; Cui Yang-yang; Wang Lei; Ma Shuang-ping; Li Zhi-chao; Feng Hui-gen

doi:10.3969/j.issn.2095-4344.2015.07.005

Abstract：BACKGROUND:Oligodendrocytes are mainly differentiated from oligodendrocyte precursor cel s and the differentiation is tightly regulated by various factors. Some cyclin-dependent kinases play pivotal roles in oligodendrocyte precursor cel differentiation due to their regulation on the early stage of differentiation. <br> OBJECTIVE:To investigate the potential role of a newly identified cyclin-dependent kinase-like protein, PFTK1 in differentiation and also study the related mechanisms. <br> METHODS:siRNA technology and western blot assay were used to examine the differentiation markers of OLN-93 and the activation condition of corresponding signal pathways. <br> RESULTS AND CONCLUSION:With serum-deprivation, OLN-93 underwent differentiation simultaneously. When PFTK1 was silenced by siRNA technology, OLN-93 differentiation was significantly improved, as judged by morphological observations. Accordingly, western blot results showed a marked increase of differentiation markers cyclic nucleotide phosphodiesterase and myelin oligodendrocyte glycoprotein in PFTK1-silenced cel s. From the study on PFTK1-related signaling pathways, we found that PFTK1 silencing induced the activation of PI3K/AKT pathway but not MAPK/ERK pathway. Furthermore, the inhibition of AKT by its specific inhibitor abrogated PFTK1 silencing-promoted OLN-93 differentiation. Taken together, our data demonstrate that PFTK1 negatively regulates OLN-93 differentiation through PI3K/AKT pathway, providing a clue for developing new therapeutic approaches to treat degenerative neurological diseases related to demyelination.