Concomitant inhibition of prolyl hydroxylases and ROCK initiates differentiation of mesenchymal stem cells and PC12 towards the neuronal lineage
Concomitant inhibition of prolyl hydroxylases and ROCK initiates differentiation of mesenchymal stem cells and PC12 towards the neuronal lineage
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DOI：
10.1016/j.bbrc.2008.09.145
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发表时间：
2008-12-12
影响因子：
3.1
通讯作者：
Bernaudin, Myriam
中科院分区：
文献类型：
--
作者：
Pacary, Emilie;Petit, Edwige;Bernaudin, Myriam
这项研究表明，脯氨酰羟化酶抑制剂FG-0041能够与ROCK抑制剂Y-27632组合，启动间充质干细胞（MSC）分化为神经元样细胞。FG-0041/Y-27632共处理引起神经元样细胞的形态学变化，增加神经元标志物表达，并引起细胞周期相关基因表达的修饰，这与MSC的细胞周期停滞一致，这三个事件显示MSC参与神经元谱系。此外，正如我们在我们以前用氯化钴和去铁胺的研究中所观察到的，Y-27632增强了这种脯氨酰羟化酶抑制剂对HIF-1的激活，这可以至少部分地解释这种共处理对MSC神经元分化的影响。此外，我们表明，这种共同治疗增强了PC 12细胞中的神经突生长和酪氨酸羟化酶表达。总之，这些结果表明，伴随抑制脯氨酰羟化酶和ROCK代表了一个相关的协议，以启动神经元分化。(C)2008年爱思唯尔公司All rights reserved.
This study demonstrates that a prolyl hydroxylase inhibitor, FG-0041, is able, in combination with the ROCK inhibitor, Y-27632, to initiate differentiation of mesenchymal stem cells (MSCs) into neuron-like cells. FG-0041/Y-27632 co-treatment provokes morphological changes into neuron-like cells, increases neuronal marker expression and Provokes modifications of cell cycle-related gene expression consistent with a cell cycle arrest of MSC, three events showing the engagement of MSC towards the neuronal lineage. Moreover, as we observed in our previous studies with cobalt chloride and desferroxamine, the activation of HIF-1 by this prolyl hydroxylase inhibitor is potentiated by Y-27632 which could explain at least in part the effect of this co-treatment on MSC neuronal differentiation. In addition, we show that this co-treatment enhances neurite outgrowth and tyrosine hydroxylase expression in PC12 cells. Altogether, these results evidence that concomitant inhibition of prolyl hydroxylases and ROCK represents a relevant protocol to initiate neuronal differentiation. (C) 2008 Elsevier Inc. All rights reserved.