MiRNA-125a-5p attenuates blood-spinal cord barrier permeability under hypoxia in vitro

Biotechnol Lett. 2020 Jan;42(1):25-34. doi: 10.1007/s10529-019-02753-8. Epub 2019 Nov 6.

Abstract

Disruption of the blood-spinal cord barrier (BSCB) results in secondary injury and apoptosis of neurons, leading to permanent neurological dysfunction after spinal cord injury. In this study, we evaluate the role of miRNA-125a-5p in the BSCB under hypoxia. The miRNA-125a-5p mimics group showed lower horseradish peroxidase (HRP) permeability and endothelial cell death rates compared with the transfection control group. By contrast, the miRNA-125a-5p inhibitor group demonstrated higher HRP permeability and endothelial cell death rates than the transfection control group. The expressions of ZO-1, occludin, VE-cadherin and their mRNA significantly increased in miRNA-125a-5p-overexpressing cells. By contrast, a remarkable reduction in ZO-1, occludin, and VE-cadherin expression and their mRNA were observed in miRNA-125a-5p-inhibited cells. MiRNA-125a-5p appears to reduce the permeability of the BSCB by up regulating the expression of ZO-1, occludin, and VE-cadherin and their mRNA, and against hypoxia-induced apoptosis of spinal cord microvascular endothelial cells. Taken together, our results clearly indicate that miRNA-125a-5p plays an important role in protecting the functions of the BSCB under hypoxia.

Keywords: Blood–spinal cord barrier (BSCB); MiRNA-125a-5p; Permeability; Spinal cord injury (SCI).

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Apoptosis
  • Blood-Brain Barrier / physiology*
  • Cadherins / metabolism
  • Endothelial Cells / physiology
  • Gene Expression Regulation
  • Hypoxia*
  • MicroRNAs / metabolism*
  • Models, Biological
  • Permeability*
  • Rats, Sprague-Dawley
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Antigens, CD
  • Cadherins
  • MIRN125 microRNA, rat
  • MicroRNAs
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • cadherin 5