Department of Neurosurgery, the Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Department of Neurosurgery, North China Oilfield General Hospital, Renqiu, 062552, Hebei, China.
Acta Neurol Belg. 2023 Aug;123(4):1321-1329. doi: 10.1007/s13760-023-02205-1. Epub 2023 Apr 5.
The abnormal expression of matrix metalloproteinase 9 (MMP9) and Aquaporin 4 (AQP4) closely associates with the traumatic brain injury (TBI) development.
Here, we investigated the relationship between miR-211-5p and MMP9/AQP4 axis in TBI patients and astrocyte cells. Demographics, clinical features, and cerebrospinal fluid (CSF) samples were collected from traumatic brain injury (TBI) patients (n = 96) and controls (n = 30) for pathological and gene expression analyses. Luciferase activity assay and gene expression analyses were performed to dissect the regulatory mechanism of miR-211-5p on MMP9/AQP4 in human astrocyte cells.
miR-211-5p mRNA was significantly decreased in the CSF of TBI patients, which positively correlated with the expression of both MMP9 and AQP4. miR-211-5p could target MMP9 directly in SVG P12 cells. Overexpression of miR-211-5p decreased the expression of MMP9, on the contrary, knockdown miR-211-5p through inhibitors increased the expression of both MMP9 and AQP4.
miR-211-5p inhibits the MMP9/AQP4 axis in human astrocyte cells, which represents a promising approach for the TBI treatment.
基质金属蛋白酶 9（MMP9）和水通道蛋白 4（AQP4）的异常表达与创伤性脑损伤（TBI）的发展密切相关。
本研究探讨了 miR-211-5p 与 TBI 患者和星形胶质细胞中 MMP9/AQP4 轴之间的关系。收集创伤性脑损伤（TBI）患者（n=96）和对照组（n=30）的人口统计学、临床特征和脑脊液（CSF）样本进行病理和基因表达分析。通过荧光素酶活性测定和基因表达分析来剖析 miR-211-5p 对人星形胶质细胞中 MMP9/AQP4 的调控机制。
TBI 患者 CSF 中的 miR-211-5p mRNA 显著降低，与 MMP9 和 AQP4 的表达呈正相关。miR-211-5p 可直接靶向 SVG P12 细胞中的 MMP9。过表达 miR-211-5p 降低了 MMP9 的表达，相反，通过抑制剂敲低 miR-211-5p 增加了 MMP9 和 AQP4 的表达。
miR-211-5p 抑制人星形胶质细胞中的 MMP9/AQP4 轴，这代表了一种有前途的 TBI 治疗方法。
