PTEN 沉默通过激活体外 PI3K/Akt/GSK3β 通路增强神经元增殖和分化。
PTEN silencing enhances neuronal proliferation and differentiation by activating PI3K/Akt/GSK3β pathway in vitro.
机构信息
Department of Orthopedics, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
出版信息
Exp Cell Res. 2018 Feb 15;363(2):179-187. doi: 10.1016/j.yexcr.2018.01.001. Epub 2018 Jan 4.
The failure of neuronal proliferation and differentiation is a major obstacle for neural repair and regeneration after traumatic central nervous system (CNS) injury. PTEN acts as an intrinsic brake on the neuronal cells, but its roles and mechanism still remain to be clarified. Herein, for the first time we confirmed that PTEN had a dual effect on the neuronal cells in vitro. Firstly, we found that PTEN knockdown significantly promoted cell proliferation and differentiation. Then, PTEN knockdown activated PI3K/Akt and Wnt/β-catenin pathways in vitro. Further evidence revealed that GSK3β as a key node involved in PTEN controlling cell proliferation and differentiation in PC12 cells. In addition, we identified that PTEN-GSK3β pathway modulated neuronal proliferation via β-catenin. Taken together, these results suggest that PTEN silencing enhances neuronal proliferation and differentiation by activating PI3K/Akt/GSK3β pathway that it may be a promising therapeutic approach for CNS injury.
神经元增殖和分化的失败是创伤性中枢神经系统 (CNS) 损伤后神经修复和再生的主要障碍。PTEN 作为神经元细胞的内在制动器，但它的作用和机制仍有待阐明。在此，我们首次证实，PTEN 在体外对神经元细胞具有双重作用。首先，我们发现 PTEN 敲低显著促进细胞增殖和分化。然后，PTEN 敲低在体外激活了 PI3K/Akt 和 Wnt/β-catenin 通路。进一步的证据表明，GSK3β 作为一个关键节点，参与了 PTEN 对 PC12 细胞增殖和分化的调控。此外，我们发现 PTEN-GSK3β 通路通过 β-catenin 调节神经元增殖。总之，这些结果表明，PTEN 沉默通过激活 PI3K/Akt/GSK3β 通路增强神经元增殖和分化，这可能是 CNS 损伤的一种有前途的治疗方法。
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