3 years ago

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

Shuxin Shen, Lixia Wang, Shoukun Ding, Yongqiang Li
Objective: This study is designed to determine whether lincRNA-DYNLRB2-2 could promote cholesterol efflux through regulating the expression of TLR2. Methods: 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. Results: 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. Conclusion: LincRNA DYN-LRB2-2 upregulates cholesterol efflux by decreasing TLR2 expression in macrophages. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26352

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