MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4

J Cell Physiol. 2018 Oct;233(10):6630-6637. doi: 10.1002/jcp.26389. Epub 2018 May 8.

Abstract

MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR-182-5p has been involved in many diseases. However, the role miR-182-5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low-density lipoprotein (ox-LDL) in RAW264.7 cells. miR-182-5p was markedly decreased in AS model dose-dependently and time-dependently. Additionally, CD36, oil-red staining levels, TC, and TG were inhibited by miR-182-5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR-182-5p inhibitors were transfected into RAW264.7 cells. It is well known that toll-like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR-182-5p. We observed TLR4 was activated in AS models and miR-182-5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR-182-5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression.

Keywords: Ox-LDL; TLR4; atherosclerosis; macrophage; miR-182-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Atherosclerosis / genetics*
  • Atherosclerosis / pathology
  • CD36 Antigens / genetics
  • Gene Expression Regulation / genetics
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Lipoproteins, LDL / genetics
  • Lipoproteins, LDL / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Oxidative Stress / genetics*
  • RAW 264.7 Cells
  • Signal Transduction / genetics
  • Toll-Like Receptor 4 / genetics*

Substances

  • CD36 Antigens
  • Lipoproteins, LDL
  • MicroRNAs
  • Mirn182 microRNA, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • oxidized low density lipoprotein