MicroRNA-23a suppresses the apoptosis of inflammatory macrophages and foam cells in atherogenesis by targeting HSP90

Gene. 2020 Mar 1:729:144319. doi: 10.1016/j.gene.2019.144319. Epub 2019 Dec 26.

Abstract

In previous study, we have found that microRNA-23a is down regulated in atherosclerotic tissues. Here we demonstrate that miR-23a directly binds to 3'UTR of HSP90 mRNA to suppress the expression of HSP90. To investigate the potential roles of miR-23a in macrophage, THP-1 macrophages were transfected with miR-23a mimics or inhibitors. Our results showed inflammatory factors IL-6 and MCP-1 concentrations in cell culture medium of macrophage and foam cell transfected with miR-23a mimics were decreased. Furthermore, we find that apoptosis of macrophage and foam cells transfected with miR-23a mimics were inhibited. Over expression of miR-23a in foam cells could reduced lipid intake and accumulation in foam cells. Meanwhile, we found that in inflammatory macrophages and foam cells transfected with miR-23a mimcs, HSP90 and NF-κB proteins are significantly decreased. Our results have suggested a promising and potential therapeutic target for atherosclerosis.

Keywords: Apoptosis; HSP90; Inflammatory response; miR-23a.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Cell Proliferation / genetics
  • Foam Cells / metabolism
  • Foam Cells / pathology*
  • HSP90 Heat-Shock Proteins / genetics*
  • Humans
  • Inflammation / genetics
  • Macrophages / metabolism
  • Macrophages / pathology*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • NF-kappa B / metabolism
  • THP-1 Cells

Substances

  • 3' Untranslated Regions
  • HSP90 Heat-Shock Proteins
  • MIRN23a microRNA, human
  • MicroRNAs
  • NF-kappa B