LincRNA DYN-LRB2-2 upregulates cholesterol efflux by decreasing TLR2 expression in macrophages

J Cell Biochem. 2018 Feb;119(2):1911-1921. doi: 10.1002/jcb.26352. Epub 2017 Nov 10.

Abstract

This study is designed to determine whether lincRNA-DYNLRB2-2 could promote cholesterol efflux through regulating the expression of TLR2. THP-1 and RAW264.7 cells were incubated with oxLDL for 48 h to induce the formation of foam cells, and ORO staining was performed and intracellular cholesterol contents were measured by HPLC assay. qRT-PCR and Western blotting were performed to detect mRNA and protein expression levels, respectively. Lentiviral vector LV-DYNLRB2-2 and lincRNA-DYNLRB2-2 siRNA was constructed to explore its potential role. The cholesterol efflux was assessed by liquid scintillation counting. The effects of TRL2 were determined in apoE-/- mice that fed a high fat diet and were randomly divided into three groups and infected with LV-Mock, LV-Sh-TRL2, or LV-TRL2. Atherosclerosis was observed in the aortic sinus and the levels of cytokines and serum biochemical parameters were measured. Ox-LDL induced foam cell formation in the THP-1 and RAW264.7 cells. LincRNA DYN-LRB2-2 was upregulated in oxLDL-treated THP-1 and Raw264.7 cells. LincRNA-DYNLRB2-2 plays important role in regulating the cholesterol efflux, ABCA1 expression level and anti-inflammatory processes in THP-1 and RAW264.7 cells. Further study indicated that lincRNA-DYNLRB2-2 negatively regulated TRL2 expression and TRL2 overexpression reversed the effects of lincRNA-DYNLRB2-2 on cholesterol efflux and ABCA1 expression level in THP-1 and RAW264.7 cells. Besides, we found TRL2 plays important role in lipid accumulation, plaque formation and regulating serum inflammatory cytokines level in apoE-/- mice with a high fat diet. LincRNA DYN-LRB2-2 upregulates cholesterol efflux by decreasing TLR2 expression in macrophages.

Keywords: LincRNA DYN-LRB2-2; TLR2 expression; atherosclerosis; cholesterol efflux.

MeSH terms

  • 3' Untranslated Regions
  • ATP Binding Cassette Transporter 1 / metabolism
  • Animals
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Cholesterol / metabolism*
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Lipoproteins, LDL / pharmacology
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Knockout, ApoE
  • RAW 264.7 Cells
  • RNA, Long Noncoding / genetics*
  • THP-1 Cells
  • Toll-Like Receptor 2 / genetics*

Substances

  • 3' Untranslated Regions
  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Lipoproteins, LDL
  • RNA, Long Noncoding
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • oxidized low density lipoprotein
  • Cholesterol