miR-155-5p in Extracellular Vesicles Derived from Choroid Plexus Epithelial Cells Promotes Autophagy and Inflammation to Aggravate Ischemic Brain Injury in Mice

Oxid Med Cell Longev. 2022 Feb 16:2022:8603427. doi: 10.1155/2022/8603427. eCollection 2022.

Abstract

Ischemic stroke is a common disease of the central nervous system, and ischemic brain injury (IBI) is its main manifestation. Recently, extracellular vesicles (EVs) have been strongly related to the diagnosis and treatment of IBI. However, the underlying mechanism of their effects remains enigmatic. In the present study, we aimed to study how miR-155-5p plays a role in choroid plexus epithelial (CPE) cell-derived EVs in IBI pathology. We found that miR-155-5p expression was enriched in CPE cell-derived EVs, which were subsequently internalized by neurons, enabling the delivery of miR-155-5p into neurons. An inducible oxygen and glucose deprivation and reoxygenation (OGD/R) cell model was developed to mimic ischemic neuronal injury in vitro. miR-155-5p overexpression led to reduced neuron viability, promoted apoptosis, elevated autophagic proteins' expression, and activated NLR family pyrin domain-containing 3- (NLRP3-) related inflammasomes, thereby aggravating OGD-induced neuronal injury. A dual-luciferase reporter assay exhibited that miR-155-5p could inhibit the Ras homolog enriched in brain (Rheb) expression, a mechanism critical for miR-155-5p-mediated neuronal injury. Furthermore, a mouse IBI model was developed using the transient middle cerebral artery occlusion (tMCAO) method. Animal experiments verified that miR-155p delivery via CPE cell-derived EVs aggravated IBI by suppressing Rheb expression. In conclusion, miR-155-5p in CPE-derived EVs can aggravate IBI pathology by suppressing Rheb expression and promoting NLRP3-mediated inflammasomes, suggesting its role as a potential therapeutic target in IBI.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Choroid Plexus / metabolism*
  • Epithelial Cells / metabolism*
  • Extracellular Vesicles / genetics
  • Extracellular Vesicles / metabolism*
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Inflammasomes / metabolism
  • Inflammation
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Ras Homolog Enriched in Brain Protein / genetics
  • Ras Homolog Enriched in Brain Protein / metabolism
  • Signal Transduction

Substances

  • Inflammasomes
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Ras Homolog Enriched in Brain Protein
  • Rheb protein, mouse