Poly-L-ornithine promotes preferred differentiation of neural stem/progenitor cells via ERK signalling pathway.
Poly-L-ornithine promotes preferred differentiation of neural stem/progenitor cells via ERK signalling pathway.
复制标题
聚-L-鸟氨酸通过 ERK 信号通路促进神经干/祖细胞的优先分化
DOI：
10.1038/srep15535
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发表时间：
2015-10-27
影响因子：
4.6
通讯作者：
Feng H
中科院分区：
文献类型：
--
作者：
Ge H;Tan L;Wu P;Yin Y;Liu X;Meng H;Cui G;Wu N;Lin J;Hu R;Feng H
神经干细胞/祖细胞（NSPCs）替代疗法是修复受损大脑最具吸引力的策略。这种疗法的主要挑战是丰富NSPCs并引导它们分化为特定的神经细胞类型。本实验研究了聚l -鸟氨酸（PO）、聚l -赖氨酸（PLL）和纤维连接蛋白（FN）三种生物材料底物对大鼠NSPCs增殖分化的影响，并探讨了其作用机制。结果表明，与PLL和FN相比，PO可显著促进NSPCs增殖并诱导其优先分化。检测几种神经细胞亚型的蛋白标记，发现PO显著诱导NSPCs表达双皮质素（DCX）和Olig2，一个用于神经母细胞和年轻神经元，另一个用于年轻少突胶质细胞。ERK拮抗剂U0126可以抑制PO的上述作用，而ERK通路激动剂Ceramide C6可以增强PO的上述作用，提示ERK信号通路参与了这一过程。鉴于神经元和少突胶质细胞在许多神经系统疾病中都是最脆弱的细胞，po诱导的向神经元和少突胶质细胞的优先分化是基于nspc的治疗的潜在范例。
Neural stem/progenitor cells (NSPCs) replacement therapies are the most attractive strategies to restore an injured brain. Key challenges of such therapies are enriching NSPCs and directing them differentiation into specific neural cell types. Here, three biomaterial substrates Poly-L-ornithine (PO), Poly-L-lysine (PLL) and fibronectin (FN) were investigated for their effects on proliferation and differentiation of rat NSPCs and the underlying mechanisms were also explored. The results showed PO significantly increased NSPCs proliferation and induced preferred differentiation, compared with PLL and FN. Checking protein markers of several neural cell subtypes, it is showed PO significantly induced NSPCs expressing Doublecortin (DCX) and Olig2, one for neuroblasts and young neurons and the other for young oligodendrocytes. It is suggested the ERK signaling pathway was involving in this process because an ERK antagonist U0126 could inhibit PO’s effects mentioned above, as well as an ERK pathway agonist Ceramide C6 could enhance them. Given that both neurons and oligodendrocytes are the most vulnerable cells in many neurological diseases, PO-induced preferred differentiation into neurons and oligodendrocytes is a potential paradigm for NSPCs-based therapies.