TGF-&amp;beta;1 Up-Regulates Expression of ABCA1, ABCG1 and SR-BI through Liver X Receptor &amp;alpha; Signaling Pathway in THP-1 Macrophage-Derived Foam Cells

Hu, Yan‐Wei; Wang, Qian; Ma, Xin; Li, Xiaoxu; Liu, Xiehong; Xiao, Ji; Liao, Duan‐Fang; Xiang, Jim; Tang, Chao-Ke

doi:10.5551/jat.3152

Cited by 68 publications

(43 citation statements)

References 36 publications

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“…This stimulation, by increasing the level of protein in the cell might contribute to the redistribution of ABCG1 from the endoplasmic reticulum or another cellular compartment (48) into the plasma membrane. TGF␤ is known to increase the expression of ABCG1, ABCA1, and cholesterol efflux in macrophage derived foam cells, with a particularly strong effect on ABCG1 (49). Because TGF␤ participates in the inhibition of macrophage foam cell formation induced by very low density lipoprotein remnants (50), these results suggest an antiatherogenic role for the TGF␤/LRP1/ Wnt5a pathway.…”

Section: Discussionmentioning

confidence: 70%

Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation

Asmar

Terrand

Jenty

et al. 2016

Journal of Biological Chemistry

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The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (␣) chain of LRP1 mediates TGF␤-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (␤) chain of LRP1 suffices to limit cholesterol accumulation in LRP1؊/؊ cells. Cholesterol is a major component of mammalian cell membranes that accumulates in the vascular wall during atherosclerosis, the leading cause of death in industrialized societies (1, 2). The low density lipoprotein receptor-related protein 1 (LRP1), 3 a cell surface receptor that belongs to the LDL receptor family, endocytoses multiple ligands (3). It consists of an 85-kDa membrane-bound carboxyl fragment (␤ chain) and a non-covalently attached 515-kDa (␣ chain) amino-terminal fragment (4). We previously demonstrated that LRP1 limits cholesterol accumulation in the arterial wall. Mice deficient for LRP1 in vascular smooth muscle cells (vSMCs) (smLRP1 mice) develop vSMCs proliferation, cholesterol accumulation (5), and massive foam cell formation when fed a cholesterol-rich diet (6 -10). Whereas LRP1 integrates the platelet-derived growth factor (PDGF-BB) (8, 9) and transforming growth factor-␤ (TGF-␤) at the plasma membrane, two pathways known to regulate vSMCs proliferation (7), the physiological importance and function of LRP1 in regulating intracellular cholesterol homeostasis is still poorly understood. Several mechanisms have been proposed. LRP1 has been shown to promote cholesterol export in vSMCs through induction of ATP binding cassette transporter A1 (ABCA1) levels (5) and to induce a Wnt5a/␤-catenin pathway to limit cholesterol overload in mouse embryonic fibroblasts (11). Moreover, smLRP1 mice express very low levels of Wnt5a in vSMCs (12). TGF-␤ also stimulates a non-canonical Wnt5a pathway in airway smooth muscle cells (13). These data strongly suggest that a TGF-␤/LRP1/Wnt5a pathway limits intracellular cholesterol accumulation.How Wnt5a interferes with cholesterol homeostasis is unknown. It might increase cholesterol export and/or block cholesterol synthesis. ABCA1 and the ATP binding cassette transporter G1 (ABCG1) are two proteins that promote cholesterol efflux. Cholesterol synthesis is tightly regulated by a feedback system that senses the level of cholesterol and modulates the transcription of genes encoding enzymes of cholesterol biosynthesis and uptake (14, 15). For instance, when cholesterol levels rise in cells, the membrane-embedded protein of the endoplasmic reticulum (ER), Scap, senses the increase and binds to Insigs, proteins located to the ER. Insigs then limit cleavage and nuclear translocation of sterol regulatory element-binding proteins (SREBPs), in particular SREBP-2, an activator of cholesterol synthesis in liver and a...

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Section: Discussionmentioning

confidence: 70%

Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation

Asmar

Terrand

Jenty

et al. 2016

Journal of Biological Chemistry

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“…Recently, we found that IFN-γ may first downregulate the expression of LXRα through the JAK/STAT1 signaling pathway and then decrease the expression of ABC-A1 in THP-1 macrophage-derived foam cells [38] . TGF-β1 upregulates the expression of ABC-A1, ABC-G1 and SR-BI via the LXRα signaling pathway in THP-1 macrophage-derived foam cells [60] . Additionally, NO-1886 increases the expression of ABC-A1 by upregulating LXRα in the livers of Chinese Bama minipigs [39] .…”

Section: Rxr and Lxrmentioning

confidence: 99%

A novel model of cholesterol efflux from lipid-loaded cells

et al. 2010

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Cholesterol efflux from lipid-loaded cells is a key athero-protective event that counteracts cholesterol uptake. The imbalance between cholesterol efflux and uptake determines the prevention or development of atherosclerosis. Many proteins and factors participate in the cholesterol efflux event. However, there are currently no systematic models of reverse cholesterol transport (RCT) that include most RCT-related factors and events. On the basis of recent research findings from other and our laboratories, we propose a novel model of one center and four systems with coupling transportation and networking regulation. This model represents a common way of cholesterol efflux; however, the systems in the model consist of different proteins/factors in different cells. In this review, we evaluate the novel model in vascular smooth muscle cells (VSMCs) and macrophages, which are the most important original cells of foam cells. This novel model consists of 1) a caveolae transport center, 2) an intracellular trafficking system of the caveolin-1 complex, 3) a transmembrane transport system of the ABC-A1 complex, 4) a transmembrane transport system of the SR-B1 complex, and 5) an extracelluar trafficking system of HDL/Apo-A1. In brief, the caveolin-1 system transports cholesterol from intracellular compartments to caveolae. Subsequently, both ABC-A1 and SR-B1 complex systems transfer cholesterol from caveolae to extracellular HDL/Apo-A1. The four systems are linked by a regulatory network. This model provides a simple and concise way to understand the dynamic process of atherosclerosis.

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“…The synthetic LXR agonist T0901317 can reduce the atherosclerotic lesion area and elevate ABCA1 gene and protein expression in apoE KO mice 35) . Our previous studies suggested that LXR was up-regulated by TGF-1 treatment, which up-regulates ABCA1 expression through the LXR pathway 27) . In the current study, our data show that ABCA1 mRNA and protein expressions were significantly up-regulated by LXR agonist 22 (R)-Hch after AOPP treatment, and LXR expression was inhibited by LXR siRNA, which increased the down-regulation of AOPPs on ABCA1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…LXR agonist promoted ABCA1 expression in apoE KO mice 26) . Transforming growth factor-beta1 (TGF-beta1) up-regulated expressions of ABCA1 through the LXR alpha pathway in THP-1 macrophage-derived foam cells 27) . The objective of this study was to investigate the effects of AOPPs on ABCA1 expression and cholesterol efflux, and to further determine the possible mechanism.…”

Section: Introductionmentioning

confidence: 99%

AOPPs Inhibits Cholesterol Efflux by Down-regulating ABCA1 Expression in a JAK/STAT Signaling Pathway-Dependent Manner

Zhang

Xiao

Liu

et al. 2011

JAT

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TGF-β1 Up-Regulates Expression of ABCA1, ABCG1 and SR-BI through Liver X Receptor α Signaling Pathway in THP-1 Macrophage-Derived Foam Cells

Cited by 68 publications

References 36 publications

Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation

Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation

A novel model of cholesterol efflux from lipid-loaded cells

AOPPs Inhibits Cholesterol Efflux by Down-regulating ABCA1 Expression in a JAK/STAT Signaling Pathway-Dependent Manner

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