miR-211-5p targeting MMP9 regulates the expressions of AQP4 in traumatic brain injury

Acta Neurol Belg. 2023 Aug;123(4):1321-1329. doi: 10.1007/s13760-023-02205-1. Epub 2023 Apr 5.

Abstract

Objective: The abnormal expression of matrix metalloproteinase 9 (MMP9) and Aquaporin 4 (AQP4) closely associates with the traumatic brain injury (TBI) development.

Methods: 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.

Results: 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.

Conclusion: miR-211-5p inhibits the MMP9/AQP4 axis in human astrocyte cells, which represents a promising approach for the TBI treatment.

Keywords: AQP4; Astrocyte cell; MMP9; Traumatic brain injury; miR-211-5p.

MeSH terms

  • Aquaporin 4 / genetics
  • Brain Injuries, Traumatic* / genetics
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • Aquaporin 4
  • Matrix Metalloproteinase 9
  • MicroRNAs
  • MIRN211 microRNA, human
  • MMP9 protein, human
  • AQP4 protein, human