Up-regulated microRNA-199b-3p represses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke through down-regulation of MAPK/ERK/EGR1 axis

Cell Cycle. 2019 Aug;18(16):1868-1881. doi: 10.1080/15384101.2019.1632133. Epub 2019 Jul 10.

Abstract

MicroRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. Therefore, the purpose of present study was to explore the effect of microRNA-199b-3p (miR-199b-3p) on the cerebral microvascular endothelial cells (CMECs) in middle cerebral artery occlusion-reperfusion (MCAO-R) mice by regulating MAPK/ERK/EGR1 axis. Mice were used to establish MCAO-R models and to measure the expression of miR-199b-3p and the MAPK/ERK/EGR1 axis-related genes. CMECs were extracted from the MCAO-R mice. A series of mimic or inhibitor for miR-199b-3p, or U0126 (an inhibitor for the MAPK/ERK/EGR1 axis) were introduced to treat these CMECs. The levels of miR-199b-3p and MAPK/ERK/EGR1 axis-related genes in tissues and cells were detected. The effects miR-199b-3p on the process of CMECs, including cell viability, cell cycle and cell apoptosis were evaluated. miR-199b-3p expressed poorly in the brain tissues after MCAO-R, along with activated MAPK/ERK/EGR1 axis and increased CMECs apoptosis. CMECs transfected with miR-199b-3p mimics and U0126 manifested with increased cell viability, more cells arrested at the S stage, and inhibited apoptosis of CMECs. In conclusion, these key results demonstrated up-regulated miR-199b-3p could protect mice against ischemic stroke by inhibiting the apoptosis of CMECs through blockade of MAPK/ERK/EGR1 axis.

Keywords: Ischemic stroke; MAPK/ERK/EGR1axis; cerebral microvascular endothelial cells; microRNA-199b-3p; middle cerebral artery occlusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Brain Ischemia / metabolism*
  • Cell Survival / genetics
  • Cerebrum / pathology*
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Endothelial Cells / metabolism*
  • MAP Kinase Signaling System / genetics*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • S Phase Cell Cycle Checkpoints / genetics
  • Stroke / metabolism*
  • Up-Regulation / genetics

Substances

  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • MicroRNAs
  • Mirn199 microRNA, mouse
  • Mitogen-Activated Protein Kinases

Grants and funding

This study was supported by National Natural Science Foundation of China [H0928].