Nuclear heme oxygenase-1 improved the hypoxia-mediated dysfunction of blood-spinal cord barrier via the miR-181c-5p/SOX5 signaling pathway.

Abstract

Our previous study demonstrated that adenovirus-delivered GFP nuclear heme oxygenase-1 (nuclear HO-1, NHO-1) fragments lacking 23 amino acids at the C-terminus (Ad-GFP-HO-1C[INCREMENT]23) showed the potential therapeutic effects mediated by its improvement of the blood-spinal cord barrier (BSCB) integrity. However, the NHO-1-mediated molecular mechanism in regulating the BSCB function remains unclear. The BSCB model in vitro was established via a coculture of primary rat brain microvascular endothelial cells (RBMECs) and spinal cord astrocytes on transwell system. NHO-1 markedly reduced the disruption of the BSCB integrity induced by hypoxia. And NHO-1 significantly attenuated the expression of miR-181c-5p, but increased the expression level of SOX5 protein. miR-181c-5p was shown as an essential miRNA for increasing the BSCB permeability under hypoxia condition. Furthermore, we identified that miR-181c-5p could regulate the expression of SOX5 through binding to the 3'-UTR of its mRNA. And the decreased BSCB permeability and upregulation of tight junction (TJ) protein expression induced by NHO-1 could be partly reversed by the inhibition of SOX5 or miR-181c-5p (+). The present study results provide a better understanding of the molecular mechanisms induced by NHO-1 in improving the BSCB integrity, which is associated with the regulation of miR-181c-5p/SOX5/TJ signaling pathway.

• Authors: Deshui Yu, Rui Sun, Dequan Shen, Lihao Ge, Tao Xue, Yang Cao
• Journal: Neuroreport (Neuroreport) Vol. 32 Issue 2 Pg. 112-120 (01 13 2021) ISSN: 1473-558X [Electronic] England
• PMID: 33290309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• MIRN181 microRNA, rat
• MicroRNAs
• Occludin
• SOXD Transcription Factors
• Tight Junction Proteins
• Tjp1 protein, rat
• Zonula Occludens-1 Protein
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Animals
• Blood (metabolism)
• Capillary Permeability
• Gene Knock-In Techniques
• Heme Oxygenase (Decyclizing) (genetics)
• Hypoxia (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• Occludin (metabolism)
• Rats
• SOXD Transcription Factors (genetics, metabolism)
• Spinal Cord (metabolism)
• Tight Junction Proteins (metabolism)
• Zonula Occludens-1 Protein (metabolism)