Peng Longying, Shu Xiaomei, Lang Changhui, Yu Xiaohua
Department of Pediatric, First Affiliated Hospital, Zunyi Medical College, Zunyi, 563003, Guizhou Province, China.
Cytotechnology. 2017 Dec;69(6):933-941. doi: 10.1007/s10616-017-0103-6. Epub 2017 Jun 10.
Cardiotrophin-1 (CT1) 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 CT1 generated more cells that were neuron-like and produced stronger expression of neural-lineage markers than cells treated with NIM and without CT1. Bcl-2 and Akt phosphorylation (p-Akt) expression levels increased significantly in cells treated with both NIM and CT1. This treatment also effectively blocked cell death following neural induction and decreased Bax, Bak and cleaved-caspase 3 expression compared with cells treated with NIM without CT1. In addition, the inhibition of phosphatidylinositol 3-kinase (PI3K) abrogated p-Akt and Bcl-2 expression. Thus, PI3K/Akt contribute to CT1-stimulated neural differentiation and to the survival of differentiated cells.
心肌营养素-1（CT1）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，我们从人脐带血间充质干细胞分化为神经元样细胞的潜能、其存活特征以及相关分子机制方面，分析了CT1对这些细胞的刺激作用。与用神经诱导培养基（NIM）处理但未用CT1处理的细胞相比，用NIM和CT1处理的细胞产生了更多的神经元样细胞，并且神经谱系标志物的表达更强。在用NIM和CT1处理的细胞中，Bcl-2和Akt磷酸化（p-Akt）表达水平显著增加。与用NIM但未用CT1处理的细胞相比，这种处理还有效阻断了神经诱导后的细胞死亡，并降低了Bax、Bak和裂解的半胱天冬酶-3的表达。此外，磷脂酰肌醇3-激酶（PI3K）的抑制消除了p-Akt和Bcl-2的表达。因此，PI3K/Akt有助于CT1刺激的神经分化以及分化细胞的存活。
