miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages

Vinod, Manjula, Chennamsetty, Indumathi, Colin, Sophie, Belloy, Loic, De Paoli, Federica, Schaider, Helmut, Graier, Wolfgang F., Frank, Saša, Kratky, Dagmar, Staels, Bart, Chinetti-Gbaguidi, Giulia and Kostner, Gerhard M. (2014) miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1841 6: 827-835. doi:10.1016/j.bbalip.2014.02.006


Author Vinod, Manjula
Chennamsetty, Indumathi
Colin, Sophie
Belloy, Loic
De Paoli, Federica
Schaider, Helmut
Graier, Wolfgang F.
Frank, Saša
Kratky, Dagmar
Staels, Bart
Chinetti-Gbaguidi, Giulia
Kostner, Gerhard M.
Title miR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages
Journal name Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids   Check publisher's open access policy
ISSN 1879-2618
1388-1981
Publication date 2014-06
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.bbalip.2014.02.006
Open Access Status DOI
Volume 1841
Issue 6
Start page 827
End page 835
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2015
Language eng
Abstract Liver X receptors (LXRα and LXRβ) are key transcription factors in cholesterol metabolism that regulate cholesterol biosynthesis/efflux and bile acid metabolism/excretion in the liver and numerous organs. In macrophages, LXR signaling modulates cholesterol handling and the inflammatory response, pathways involved in atherosclerosis. Since regulatory pathways of LXR transcription control are well understood, in the present study we aimed at identifying post-transcriptional regulators of LXR activity. MicroRNAs (miRs) are such post-transcriptional regulators of genes that in the canonical pathway mediate mRNA inactivation. In silico analysis identified miR-206 as a putative regulator of LXRα but not LXRβ. Indeed, as recently shown, we found that miR-206 represses LXRα activity and expression of LXRα and its target genes in hepatic cells. Interestingly, miR-206 regulates LXRα differently in macrophages. Stably overexpressing miR-206 in THP-1 human macrophages revealed an up-regulation and miR-206 knockdown led to a down-regulation of LXRα and its target genes. In support of these results, bone marrow-derived macrophages (BMDMs) from miR-206 KO mice also exhibited lower expression of LXRα target genes. The physiological relevance of these findings was proven by gain- and loss-of-function of miR-206; overexpression of miR-206 enhanced cholesterol efflux in human macrophages and knocking out miR-206 decreased cholesterol efflux from MPMs. Moreover, we show that miR-206 expression in macrophages is repressed by LXRα activation, while oxidized LDL and inflammatory stimuli profoundly induced miR-206 expression. We therefore propose a feed-back loop between miR-206 and LXRα that might be part of an LXR auto-regulatory mechanism to fine tune LXR activity.
Keyword Micro-RNA
ox-LDL
LXR target gene
ABC
ApoA-I
HDL
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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