Correlation between mechanism of oxidized-low density lipoprotein-induced macrophage apoptosis and inhibition of target gene platelet derived growth factor receptor-β expression by microRNA-9

Bioengineered. 2021 Dec;12(2):11716-11725. doi: 10.1080/21655979.2021.2006864.

Abstract

This study was to explore the effects of oxidized-low density lipoprotein (ox-LDL) on the proliferation and apoptosis of macrophages, and the role of miRNA-9 in the targeted regulation of platelet-derived growth factor receptor-β (PDGFR-β) expression. Macrophage RAW264.7 cells were cultured and foamed with 100 mg/L ox-LDL to detect the cell proliferation and apoptosis and target protein expression levels. Subsequently, the miRNA-9 mimics and inhibitors were transfected to detect the expression level of PDGFR-β. The dual-luciferase reporter gene was predicted and applied to detect the target-binding effect of miRNA-9 and PDGFR-β in the cells. The results showed that ox-LDL could induce the foaming of macrophages RAW264.7, inhibit the cell proliferation, and promote the cell apoptosis. After ox-LDL induction, expression of Caspase-3 in macrophages RAW264.7 was up-regulated, and that of glucose regulated protein 78 was down-regulated. The transfection of miRNA-9 mimics could greatly inhibit the expression of PDGFR-β mRNA and proteins in the cells. In addition, the results of the dual-luciferase reporter gene showed that the ratio of luciferase activity was significantly reduced after the miRNA-9 mimic and the wild-type PDGFR-β plasmid were co-transfected. In summary, ox-LDL could induce foaming of macrophages and promote cell apoptosis, and miRNA-9 could target and bind to the 3'UTR region of PDGFR-β, thereby inhibiting the gene expression.

Keywords: Oxidized-low density lipoprotein; macrophages; microRNA-9; platelet derived growth factor receptor-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Base Sequence
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • Endoplasmic Reticulum Chaperone BiP / metabolism
  • Genes, Reporter
  • Lipoproteins, LDL / pharmacology*
  • Luciferases / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Platelet-Derived Growth Factor / genetics*
  • Receptors, Platelet-Derived Growth Factor / metabolism

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • Hspa5 protein, mouse
  • Lipoproteins, LDL
  • MIRN9 microRNA, mouse
  • MicroRNAs
  • RNA, Messenger
  • oxidized low density lipoprotein
  • Luciferases
  • Receptors, Platelet-Derived Growth Factor
  • Caspase 3

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.