Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

Sallam, Tamer; Jones, Michael Owen; Thomas, Brandon J.; Wu, Xiaohui; Gilliland, Thomas; Qian, Kevin; Eskin, Ascia; Casero, David; Zhang, Zhengyi; Sandhu, Jaspreet; Salisbury, David; Rajbhandari, Prashant; Civelek, Mete; Hong, Cynthia; Ito, Ayaka; Liu, Xin; Dániel, Bence; Lusis, Aldons J.; Whitelegge, Julian P.; Nagy, László; Castrillo, Antonio; Smale, Stephen T.; Tontonoz, Peter

doi:10.1038/nm.4479

Cited by 182 publications

(160 citation statements)

References 50 publications

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“…(B) ChIP-Seq bedgraph of LXRα and LXRβ binding patterns in mouse macrophages at the promoter region of the Gramd1b locus (Sallam et al, 2018; Sallam et al, 2016; Zhang et al, 2017). Input (Ctrl) served as a control for LXR enrichment.…”

Section: Figurementioning

confidence: 99%

Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells

Sandhu

Fairall

et al. 2018

Cell

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215

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The mechanisms underlying sterol transport in mammalian cells are poorly understood. In particular, how cholesterol internalized from HDL is made available to the cell for storage or modification is unknown. Here, we describe three ER-resident proteins (Aster-A, -B, -C) that bind cholesterol and facilitate its removal from the plasma membrane. The crystal structure of the central domain of Aster-A broadly resembles the sterol-binding fold of mammalian StARD proteins, but sequence differences in the Aster pocket result in a distinct mode of ligand binding. The Aster N-terminal GRAM domain binds phosphatidylserine and mediates Aster recruitment to plasma membrane-ER contact sites in response to cholesterol accumulation in the plasma membrane. Mice lacking Aster-B are deficient in adrenal cholesterol ester storage and steroidogenesis because of an inability to transport cholesterol from SR-BI to the ER. These findings identify a nonvesicular pathway for plasma membrane to ER sterol trafficking in mammals.

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Section: Figurementioning

confidence: 99%

Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells

Sandhu

Fairall

et al. 2018

Cell

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215

296

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“…Macrophage cholesterol efflux is mediated mainly by the cholesterol transporters ATP-binding cassette transporter (ABC)-A1 and ABCG1 (4). The expression of these transporters is tightly regulated by transcription factors (TFs), such as liver X receptors (LXRs) and peroxisome proliferator activated receptor g (PPARg) (5)(6)(7)(8); by coregulators, such as nuclear receptor corepressor 1 (NCOR1) and nuclear receptor coactivator 5 (NCOA5) (9,10); and by long, noncoding RNAs, such as macrophage-expressed LXR-induced sequence (MeXis), that specifically regulate LXR-dependent Abca1 expression (11). Macrophage ABCA1 is also involved in inflammatory regulation, as macrophage-specific Abca1 or Abcg1 knockout (KO) mice display decreased cholesterol efflux and enhanced proinflammatory gene expression (12)(13)(14).…”

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confidence: 99%

G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

et al. 2018

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Macrophages play important roles in linking alterations of cholesterol metabolism and inflammation to the development of atherosclerosis. Previous studies have identified several positive and negative crosstalk mechanisms that connect cholesterol efflux and inflammation at the transcriptional level. Of particular relevance is that the expression of ATP‐binding cassette transporter A1 (Abca1), a main regulator of cholesterol efflux, can be induced by oxysterol receptor LXR agonists but also by bacterial endotoxins, such as LPS, that activate TLR4 signaling. However, the extent to which these pathways influence each other has remained incompletely understood. We investigated the possible role of the transcriptional coregulator G protein pathway suppressor 2 (GPS2) in LPS‐induced Abca1 expression and cholesterol efflux in mouse and human macrophages. To activate Abca1, GPS2 cooperates with the LPS‐inducible NF‐κB subunit p65, but not with LXRs nor with corepressor complex subunits that otherwise cooperate with GPS2 to repress proinflammatory gene expression. Overall, our work identifies a regulatory chromatin component of crosstalk mechanisms between cholesterol efflux and inflammation that specifically affects ABCA1. Because GPS2 expression is down‐regulated in some humans with obese and type 2 diabetes, the macrophage GPS‐2/ABC‐A1 pathway could be altered and contribute to atherogenesis.—Huang, Z., Liang, N., Damdimopoulos, A., Fan, R., Treuter, E. G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages. FASEB J. 33, 1631–1643 (2019). http://www.fasebj.org

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“…Lack of MeXis in mouse BMDMs affected the structure of the Abca1 loci, had a negative impact on cholesterol overload and promoted plaque formation. Mechanically, the transcriptional coactivator DDX17 was recruited to the promoter of MeXis and magnified the LXR‐dependent transcription of Abca1 . Work by Chen et al showed that lncRNA GAS5 was highly expressed not only in the plaque of atherosclerosis patients but also in animal models.…”

Section: Inflammatory Diseases Induced By Dysregulation Of Lncrnas Anmentioning

confidence: 99%

Long non‐coding RNA expressed in macrophage co‐varies with the inflammatory phenotype during macrophage development and polarization

Xie

Wang

Tian

et al. 2019

J Cellular Molecular Medi

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Advances in microarray, RNA‐seq and omics techniques, thousands of long non‐coding RNAs (lncRNAs) with unknown functions have been discovered. LncRNAs have presented a diverse perspective on gene regulation in diverse biological processes, especially in human immune response. Macrophages participate in the whole phase of immune inflammatory response. They are able to shape their phenotype and arouse extensive functional activation after receiving physiological and pathological stimuli. Emerging studies indicated that lncRNAs participated in the gene regulatory network during complex biological processes of macrophage, including macrophage‐induced inflammatory responses. Here, we reviewed the existing knowledges of lncRNAs in the processes of macrophage development and polarization, and their roles in several different inflammatory diseases. Specifically, we focused on how lncRNAs function in macrophage, which might help to discover some potential therapeutic targets and diagnostic biomarkers.

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Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA

Cited by 182 publications

References 50 publications

Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells

Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells

G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

Long non‐coding RNA expressed in macrophage co‐varies with the inflammatory phenotype during macrophage development and polarization

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