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Ginsenoside Rg1 Regulates the Activation of Astrocytes Through <scp>lncRNA</scp>‐Malat1/<scp>miR</scp>‐124‐3p/Lamc1 Axis Driving <scp>PI3K</scp>/<scp>AKT</scp> Signaling Pathway, Promoting the Repair of Spinal Cord Injury

Yin Zhu, Wenjun Zou, Baihan Sun, Kelv Shen, Feiyun Xia, Hao Wang, Fengxian Jiang, Zhengfeng Lu

2024CNS Neuroscience & Therapeutics9 citationsDOIOpen Access PDF

Abstract

AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Topics & Concepts

PI3K/AKT/mTOR pathwayMALAT1Protein kinase BChemistryWestern blotSignal transductionCell biologyDownregulation and upregulationBiologyBiochemistryLong non-coding RNAGeneGinseng Biological Effects and ApplicationsCervical and Thoracic MyelopathyMicroRNA in disease regulation