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微小RNA-124促进骨髓间充质干细胞分化为神经源性细胞以加速脊髓损伤的恢复。

MiR-124 promotes bone marrow mesenchymal stem cells differentiation into neurogenic cells for accelerating recovery in the spinal cord injury.

作者信息

Zhao Yong, Jiang Hui, Liu Xin-Wei, Xiang Liang-Bi, Zhou Da-Peng, Chen Jian-Ting

机构信息

Department of Orthopedics, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong Province, China.

Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA, Shenyang 110016, Liaoning Province, China.

出版信息

Tissue Cell. 2015 Apr;47(2):140-6. doi: 10.1016/j.tice.2015.01.007. Epub 2015 Feb 2.

Abstract

In this research, mouse BMMSCs were isolated from bone marrow, induced to differentiate into neurogenic cells in vitro, and transplanted into the injured spinal cord after over-expression of miR-124. The results showed that the BMMSCs could induce the differentiation to neurogenic cells under the special condition medium, but when the miR-124 was over-expressed, the differentiation efficiency of neurogenic cells from BMMSCs could be promoted. This reason was demonstrated that polypyrimidine tract-binding protein 1 (PTBP1) showed a repressor for polypyrimidine tract-binding protein 2 (PTBP2) during neuronal differentiation, miR-124 reduces PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. miR-124 promoted neurogenic cells from BMMSCs were successful colonized into injured spinal cord for participation in tissue-repair. In conclusion, our research shows that the miR-124 promoted the differentiation of neuronal cells from BMMSCs, and this mechanism was miR-124 reduced the expression of PTBP1, increased the expression of PTBP2.

摘要

在本研究中,从小鼠骨髓中分离出骨髓间充质干细胞(BMMSCs),在体外诱导其分化为神经源性细胞,并在过表达miR-124后将其移植到受损脊髓中。结果表明,BMMSCs在特定条件培养基下可诱导分化为神经源性细胞,但当miR-124过表达时,可提高BMMSCs向神经源性细胞的分化效率。其原因在于,在神经元分化过程中,多嘧啶序列结合蛋白1(PTBP1)对多嘧啶序列结合蛋白2(PTBP2)起抑制作用,miR-124降低PTBP1水平,导致正确剪接的PTBP2 mRNA积累以及PTBP2蛋白显著增加。过表达miR-124促进BMMSCs来源的神经源性细胞成功定植于受损脊髓并参与组织修复。总之,我们的研究表明,miR-124促进了BMMSCs向神经元细胞的分化,其机制是miR-124降低了PTBP1的表达,增加了PTBP2的表达。

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