Protective effects of microRNA-431 against cerebral ischemia-reperfusion injury in rats by targeting the Rho/Rho-kinase signaling pathway

J Cell Physiol. 2018 Aug;233(8):5895-5907. doi: 10.1002/jcp.26394. Epub 2018 Mar 7.

Abstract

This study investigates the protective effects of miR-431 against cerebral ischemia-reperfusion injury through the Rho/Rho-kinase signaling pathway. SD rats were randomly classified into normal, sham, and model (middle cerebral artery occluded) groups. Rho expression and cerebral infarction were visualized by immunohischemistry and TTC staining, respectively. qRT-PCR and western blotting were used to measure mRNA and protein expression of miR-431 and Rho/Rho-kinase signaling pathway-related genes. Hippocampal neurons were extracted and assigned into normal, blank, negative control (NC), miR-431 mimics, miR-431 inhibitors, siRNA-Rho, and miR-431 inhibitors + siRNA-Rho groups. Proliferation and apoptosis were detected by MTT and flow cytometry, respectively. Compared with the normal group, the model group showed elevated Rho expression, area of cerebral infarction, and expressions of Rho/Rho-kinase related genes but reduced miR-431 expression. Compared with the blank group, expression of Rho, Rho-kinase α, and Rho-kinase β decreased and miR-431 expression increased in the miR-431 mimics and siRNA-Rho groups, and the tendency reversed in the miR-431 inhibitors group. Enhanced proliferation and inhibited apoptosis were exhibited in the miR-431 mimics and siRNA-Rho groups while results in the miR-431 inhibitors group reversed. Findings obtained from this study indicated that miR-431 confers protection against cerebral ischemia-reperfusion injury through negatively regulating the Rho/Rho-kinase signaling pathway.

Keywords: Rho/Rho-kinase signaling pathway; apoptosis; cerebral ischemia-reperfusion injury; microRNA-431; proliferation.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cerebral Infarction / pathology
  • Cerebral Infarction / prevention & control*
  • Disease Models, Animal
  • Hippocampus / cytology
  • Hippocampus / pathology*
  • Male
  • MicroRNAs / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / genetics
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • rho-Associated Kinases