Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.
CNS Neurosci Ther. 2024 Nov;30(11):e70103. doi: 10.1111/cns.70103.
To investigate the regulation of ginsenoside Rg1 on the PI3K/AKT pathway through the lncRNA-Malat1/miR-124-3p/ Laminin gamma1 (Lamc1) axis, activating astrocytes (As) to promote the repair of spinal cord injury (SCI).
Bioinformatics analysis was used to predict miRNA targeting Lamc1 and lncRNA targeting miR-124-3p, which were then validated through a dual-luciferase assay. Following transfection, the relationships between Malat1, miR-124-3p, and Lamc1 expression levels were assessed by qRT-PCR and Western blot (WB). Immunofluorescence staining and immunohistochemistry were utilized to measure Lamc1 expression, while changes in cavity area were observed through hematoxylin-eosin (HE) staining. Basso-Beattie-Bresnahan (BBB) scale and footprint analysis were used to evaluate functional recovery. WB was performed to assess the expression of PI3K/AKT pathway-related protein.
Rg1 was found to upregulate Malat1 expression, which in turn modulated the Malat1/miR-124-3p/Lamc1 axis. Furthermore, Rg1 activated the PI3K/Akt signaling pathway, significantly reducing the SCI cavity area and improving hind limb motor function. However, knockout of Malat1 hindered these effects, and inhibition of miR-124-3p reversed the silencing effects of Malat1.
Rg1 can induce Malat1 expression to activate the Lamc1/PI3K/AKT signaling pathway by sponging with miR-124-3p, thereby regulating As activity to repair SCI.
通过长链非编码 RNA（lncRNA）-MALAT1/miR-124-3p/层粘连蛋白γ1（Lamc1）轴研究人参皂苷 Rg1 对 PI3K/AKT 通路的调节作用，激活星形胶质细胞（As）促进脊髓损伤（SCI）的修复。
通过生物信息学分析预测靶向 Lamc1 的 miRNA 和靶向 miR-124-3p 的 lncRNA，然后通过双荧光素酶报告基因实验验证。转染后，通过 qRT-PCR 和 Western blot（WB）评估 Malat1、miR-124-3p 和 Lamc1 表达水平之间的关系。免疫荧光染色和免疫组织化学用于测量 Lamc1 的表达，通过苏木精-伊红（HE）染色观察腔面积的变化。Basso-Beattie-Bresnahan（BBB）评分和足迹分析用于评估功能恢复情况。WB 用于评估 PI3K/AKT 通路相关蛋白的表达。
Rg1 被发现上调 Malat1 的表达，进而调节 Malat1/miR-124-3p/Lamc1 轴。此外，Rg1 激活了 PI3K/Akt 信号通路，显著减少 SCI 腔面积，改善后肢运动功能。然而，敲除 Malat1 会阻碍这些作用，抑制 miR-124-3p 逆转了 Malat1 的沉默作用。
Rg1 可以通过与 miR-124-3p 结合诱导 Malat1 表达，激活 Lamc1/PI3K/AKT 信号通路，从而调节 As 活性修复 SCI。
