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微小RNA-21通过调节转化生长因子-β信号通路来调控脊髓损伤急性期后星形胶质细胞反应。

microRNA-21 regulates astrocytic reaction post-acute phase of spinal cord injury through modulating TGF-β signaling.

作者信息

Liu Ronghan, Wang Wenzhao, Wang Shuya, Xie Wei, Li Hongfei, Ning Bin

机构信息

Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.

Affiliated Hospital of Taishan Medical University, Taian, Shandong 271000, China.

出版信息

Aging (Albany NY). 2018 Jun 23;10(6):1474-1488. doi: 10.18632/aging.101484.

Abstract

Astrogliosis following spinal cord injury (SCI) was considered as a negative factor for neural regeneration. We found that miR-21 was significantly upregulated after SCI. So, we aim to determine whether miR-21 acts in a positive manner post SCI. , we measured the proliferation, apoptosis and cytokine secretion of primary cultured astrocytes after modulating the expression of miR-21 by western blot, RT-PCR and immunofluorescence. , we performed a modified Allen's weight drop model. Manipulation of the miR-21 expression level was achieved by interfering with antagomir and agomir. Clinic score was evaluated and recorded every day. Then, western blot, immunohistochemistry, TUNEL assay and ELISA were performed to detect pathological and functional alterations. Our results demonstrate that miR-21 can modulate the secretion, proliferation and apoptosis of astrocytes to promote recovery after SCI both and . These effects are likely mediated through transforming growth factor beta mediated targeting of the PI3K/Akt/mTOR pathway. These data suggest that miR-21 can regulate astrocytic function, then promote the functional recovery after SCI. We therefore highlight the positive effects of miR-21 after SCI.

摘要

脊髓损伤(SCI)后的星形胶质细胞增生被认为是神经再生的一个负面因素。我们发现脊髓损伤后miR-21显著上调。因此,我们旨在确定miR-21在脊髓损伤后是否发挥积极作用。我们通过蛋白质印迹法、逆转录-聚合酶链反应(RT-PCR)和免疫荧光法调节miR-21的表达后,检测原代培养星形胶质细胞的增殖、凋亡和细胞因子分泌。我们进行了改良的艾伦氏重物坠落模型。通过干扰抗miR和模拟miR实现对miR-21表达水平的操控。每天评估并记录临床评分。然后,进行蛋白质印迹法、免疫组织化学、TUNEL检测和酶联免疫吸附测定(ELISA)以检测病理和功能改变。我们的结果表明,miR-21可以调节星形胶质细胞的分泌、增殖和凋亡,从而在体内和体外促进脊髓损伤后的恢复。这些作用可能是通过转化生长因子β介导的PI3K/Akt/mTOR信号通路的靶向作用来介导的。这些数据表明,miR-21可以调节星形胶质细胞功能,进而促进脊髓损伤后的功能恢复。因此,我们强调了脊髓损伤后miR-21的积极作用。

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