Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways
Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways
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DOI：
10.1002/jnr.21669
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发表时间：
2008-08-01
影响因子：
4.2
通讯作者：
Jeun, Sin-Soo
中科院分区：
文献类型：
--
作者：
Lim, Jung Yeon;Park, Sane In;Jeun, Sin-Soo
脑源性神经营养因子（BDNF）在神经干细胞的分化、发育和存活中发挥着重要作用。在本研究中，我们分析了其对人脐带血间充质干细胞的刺激作用，包括其分化为神经元样细胞的潜力、其生存特征以及所涉及的分子机制。与用 NIM 和 BDNF 处理的细胞相比，用神经诱导培养基 (NIM) 和 BDNF 处理的细胞产生了更多的神经元样细胞，并且神经谱系标记物的表达更强。在用 NIM 和 BDNF 处理的细胞中，Raf-1 和 ERK 磷酸化以及 p35 表达水平显着增加。与用不含 BDNF 的 NIM 处理的细胞相比，这种处理还有效地阻止了神经诱导后的细胞死亡，并增加了 Akt 磷酸化和 Bcl2 表达。抑制 ERK 可以抑制 BDNF 刺激的 p35 和 Bcl2 上调。此外，抑制 PI3K 会消除 Akt 磷酸化和 Bcl2 表达，但不会消除 p35 表达。因此，MAPK/ERK依赖性p35上调以及MAPK/ERK依赖性和PI3K/Akt依赖性Bcl2上调有助于BDNF刺激的神经分化和分化细胞的存活。 (c) 2008 年 Wiley-Liss, Inc.
Brain-derived neurotrophic factor (BDNF) plays an important role in the differentiation, development, and survival of neural stem cells. In this study, we analyzed its effects on the stimulation of human umbilical cord blood-derived mesenchymal stem cells in terms of their potential to differentiate into neuron-like cells, their survival characteristics, and the molecular mechanisms involved. The treatment of cells with neural induction medium (NIM) and BDNF generated more cells that were neuron-like and produced stronger expression of neural-lineage markers than cells treated with NIM and without BDNF. Raf-1 and ERK phosphorylation and p35 expression levels increased significantly in cells treated with both NIM and BDNF This treatment also effectively blocked cell death following neural induction and increased Akt phosphorylation and Bcl2 expression compared with cells treated with NIM without BDNF. Inhibition of ERKs inhibited the BDNF-stimulated up-regulation of p35 and Bcl2. In addition, the inhibition of PI3K abrogated Akt phosphorylation and Bcl2 expression, but not p35 expression. Thus, MAPK/ERK-dependent p35 up-regulation and MAPK/ERK-dependent and PI3K/Akt-dependent Bcl2 up-regulation contribute to BDNF-stimulated neural differentiation and to the survival of differentiated cells. (c) 2008 Wiley-Liss, Inc.