Xu Dan, Liu Zhaoyu, Wang Shang, Peng Yan, Sun Xiaochuan
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing, 400016, PR China.
Biochem Biophys Res Commun. 2017 Aug 26;490(3):670-675. doi: 10.1016/j.bbrc.2017.06.099. Epub 2017 Jun 17.
Many degenerative diseases of the central nervous system are associated with demyelination. Oligodendrocyte progenitor cells (OPCs) are potential stem cells that can differentiate into various cell types, including oligodendrocytes (OLs). Promoting the proliferation and differentiation of OPCs into mature OLs that can myelinate axons is the key to stimulate remyelination. Here, we report that astrocytes (ASTs) increase the number of sphingosine-1-phosphate receptors 3 (S1pR3) on OPCs and promote OPCs proliferation through a direct contact via connexin 47 (Cx47). Our results demonstrate that ASTs can regulate the proliferation of OPCs through Cx47-mediated induction of S1pR3 expression on OPCs. Cx47/S1pR3 remarkably increases the number of OPCs and promotes cell transition from the G1 to the S phase. Furthermore, inhibiting either Cx47 or S1pR3 decreases OPC proliferation. In summary, ASTs regulate the expression of S1pR3 in OPCs via Cx47, which could be a valuable approach for promoting OPC proliferation. This strategy may therefore represent a potential treatment for neurological diseases caused by OLs death and demyelination.
许多中枢神经系统退行性疾病都与脱髓鞘有关。少突胶质前体细胞（OPCs）是一种潜在的干细胞，能够分化为包括少突胶质细胞（OLs）在内的多种细胞类型。促进OPCs增殖并分化为能够使轴突髓鞘化的成熟OLs是刺激髓鞘再生的关键。在此，我们报告星形胶质细胞（ASTs）通过连接蛋白47（Cx47）直接接触增加OPCs上鞘氨醇-1-磷酸受体3（S1pR3）的数量，并促进OPCs增殖。我们的结果表明，ASTs可通过Cx47介导诱导OPCs上S1pR3表达来调节OPCs增殖。Cx47/S1pR3显著增加OPCs数量，并促进细胞从G1期过渡到S期。此外，抑制Cx47或S1pR3均可降低OPCs增殖。总之，ASTs通过Cx47调节OPCs中S1pR3的表达，这可能是促进OPCs增殖的一种有效方法。因此，该策略可能代表一种针对由OLs死亡和脱髓鞘引起的神经疾病的潜在治疗方法。
