Publications by authors named "Xiaoye Zhou"

10 Publications

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Study of the mechanism underlying hsa-miR338-3p downregulation to promote fibrosis of the synovial tissue in osteoarthritis patients.

Mol Biol Rep 2019 Feb 27;46(1):627-637. Epub 2018 Nov 27.

Department of Orthopaedics, Yancheng City No. 1 People's Hospital, Yancheng, 224006, China.

Osteoarthritis (OA) is a degenerative joint disease characterized by the degradation of joint cartilage, the formation of osteophyma at joint margins, and synovial changes. Whereas lesions of the joint cartilage were the key point of the research and treatment of osteoarthritis before, a recent study showed that the synovium plays a crucial role in the pathological progress of OA. The inflammatory environment in the joints of OA patients always results in the overactivation of fibroblast-like synoviocytes (FLSs), which produce a multitude of inflammatory factors and media, not only leading to the degradation and injury of the cartilage tissue and promoting the development of osteoarthritis but also resulting in synovial fibrosis and joint stiffness. Therefore, the synovium has attracted increasing attention in the research of OA, and the study of the mechanism of activation of FLSs and the fibrosis of joint synovium may shed new light on OA treatment. By using high-throughput screening, we have identified that hsa-miR338-3p is significantly downregulated in the synovial tissue and joint effusion from OA patients. A functional study showed that overexpression of hsa-miR338-3p in the FLSs inhibited the TGF-β1-induced overactivation of the TGF-β/Smad fibrosis regulation pathway by suppressing TRAP-1 expression and thus reducing the TGF-β1-induced activation of the FLSs and the expression of vimentin and collagen I, two fibrosis markers. Meanwhile, a mechanism study also showed that the upregulation of hsa-miR338-3p reduced Smad2/3 phosphorylation by suppressing TRAP-1 and thus inhibited the TGF-β/Smad pathway and TIMP1, a downstream protein. The present study, for the first time, illustrates the role of hsa-miR338-3p in synovial fibrosis in OA patients and the related mechanism, which is of importance to the treatment of OA and its complications by targeting the FLSs and synovial tissue. Hsa-miR338-3p not only has the potential to be a target for the gene therapy of OA but also has the potential to be a new marker for the diagnosis of clinical progression in OA patients.
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http://dx.doi.org/10.1007/s11033-018-4518-8DOI Listing
February 2019

Discovering a First-Order Phase Transition in the Li-CeO System.

Nano Lett 2017 02 5;17(2):1282-1288. Epub 2017 Jan 5.

Shanghai University Materials Genome Institute and Shanghai Materials Genome Institute, Shanghai University , 99 Shangda Road, Shanghai 200444, China.

An in-depth understanding of (de)lithiation induced phase transition in electrode materials is crucial to grasp their structure-property relationships and provide guidance to the design of more desirable electrodes. By operando synchrotron XRD (SXRD) measurement and Density Functional Theory (DFT) based calculations, we discover a reversible first-order phase transition for the first time during (de)lithiation of CeO nanoparticles. The LiCeO compound phase is identified to possess the same fluorite crystal structure with FM3M space group as that of the pristine CeO nanoparticles. The SXRD determined lattice constant of the LiCeO compound phase is 0.551 nm, larger than that of 0.541 nm of the pristine CeO phase. The DFT calculations further reveal that the Li induced redistribution of electrons causes the increase in the Ce-O covalent bonding, the shuffling of Ce and O atoms, and the jump expansion of lattice constant, thereby resulting in the first-order phase transition. Discovering the new phase transition throws light upon the reaction between lithium and CeO, and provides opportunities to the further investigation of properties and potential applications of LiCeO.
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http://dx.doi.org/10.1021/acs.nanolett.6b05126DOI Listing
February 2017

Regulation of inflammatory response in human chondrocytes by lentiviral mediated RNA interference against S100A10.

Inflamm Res 2012 Nov 14;61(11):1219-27. Epub 2012 Jul 14.

Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Objective: The aim of the present study was to evaluate the effects of S100A10 silencing on the inflammatory response in human chondrocytes (HCs).The inflammation induced by lipopolysaccharide (LPS) was investigated in HCs in which the S100A10 was blocked with a lentiviral shRNA vector.

Methods: A lentiviral shRNA vector targeting S100A10 was constructed and packaged to effectively block S100A10 expression in HCs. HCs were infected with the lentivirus. S100A10 expression levels in HCs were detected by western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was employed to evaluate the change of cytokine secretion levels. The effects of S100A10 silencing on the activation of mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathway were also determined by western blot analysis. In addition, fluo-3-AM was used to demonstrate the change in calcium mobilization.

Results: Lentivirus effectively infected the HCs and inhibited the expression of S100A10. HCs with downregulated S100A10 showed significantly decreased production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10. S100A10 silencing markedly suppressed the activation of MAPKs induced by LPS. Furthermore, the calcium concentration increase in HCs stimulated by LPS was also inhibited by S100A10 knockdown.

Conclusion: Our investigation demonstrated that S100A10 might be considered as a potential target for anti-inflammatory treatment.
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http://dx.doi.org/10.1007/s00011-012-0519-6DOI Listing
November 2012

Statins synergize dexamethasone-induced adipocyte fatty acid binding protein expression in macrophages.

Atherosclerosis 2012 Jun 27;222(2):434-43. Epub 2012 Mar 27.

College of Life Sciences, Nankai University, Tianjin, China.

Objective: Macrophage adipocyte fatty acid binding protein (FABP4) plays an important role in the development of atherosclerosis. We previously reported that dexamethasone induces macrophage FABP4 mRNA expression. Statins inhibit FABP4 expression. However, it remains unknown that if statins can antagonise dexamethasone-induced macrophage FABP4 expression.

Methods And Results: We determined the effect of co-treatment of statins and dexamethasone on macrophage FABP4 expression. Unexpectedly, statins did not block the induction of macrophage FABP4 expression by dexamethasone. In contrast, statins synergized dexamethasone-induced FABP4 expression. In vivo, pitavastatin synergized dexamethasone-induced FABP4 expression in both peritoneal macrophages and adipose tissues. Cholesterol and mevalonate, but not farnesylation and geranylgeranylation, inhibited the synergistic induction. Promoter assay disclosed a putative negative glucocorticoid regulatory element (nGRE) in FABP4 gene. Pitavastatin had little effect on expression of glucocorticoid receptor (GR). However, pitavastatin enhanced dexamethasone-mediated GR nuclear translocation but inhibited the binding of GR with nGRE.

Conclusion: Our study defines an important mechanism involved in the regulation of macrophage FABP4 expression by a glucocorticoid and statins.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.03.007DOI Listing
June 2012

Induction of macrophage scavenger receptor type BI expression by tamoxifen and 4-hydroxytamoxifen.

Atherosclerosis 2011 Oct 18;218(2):435-42. Epub 2011 Jul 18.

College of Life Sciences, Nankai University, Tianjin, China.

Objective: Scavenger receptor type BI (SR-BI) is an HDL receptor that is expressed by macrophages. SR-BI expression is tightly linked to the development of atherosclerosis. Tamoxifen has been shown to be atheroprotective. However, the involved mechanisms have not been fully elucidated.

Methods And Results: In this study, we investigated the effect of tamoxifen and 4-hydroxytamoxifen on macrophage SR-BI expression. Macrophage cell lines and peritoneal macrophages isolated from wild-type mice were used to determine changes in SR-BI mRNA and protein expression in response to tamoxifen and 4-hydroxytamoxifen. We observed that tamoxifen and 4-hydroxytamoxifen increased SR-BI protein expression in a macrophage cell line derived from female mice (J774 cells) but not in a line derived from male mice (RAW cells). Similar observations were obtained in primary macrophages isolated from wild-type male and female mice. Thus, the induction of macrophage SR-BI expression by tamoxifen and 4-hydroxytamoxifen is sex-dependent. Furthermore, we observed that SR-BI expression was induced by activating the oestrogen receptor (ER, specifically ERα) but was inhibited by inactivating the ER. However, the increased macrophage SR-BI protein expression was independent of transcription because SR-BI mRNA expression and promoter activity were not influenced by tamoxifen and 4-hydroxytamoxifen. Instead, tamoxifen increased the stability of macrophage SR-BI protein. Tamoxifen administration to mice had no effect on hepatic SR-BI protein expression but improved the serum lipid profile.

Conclusion: Our study demonstrates that tamoxifen and 4-hydroxytamoxifen induce macrophage SR-BI protein expression via a post-transcriptional mechanism.
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http://dx.doi.org/10.1016/j.atherosclerosis.2011.06.048DOI Listing
October 2011

Inhibition of ERK1/2 and activation of liver X receptor synergistically induce macrophage ABCA1 expression and cholesterol efflux.

J Biol Chem 2010 Feb 25;285(9):6316-26. Epub 2009 Dec 25.

Colleges of Life Sciences, Nankai University, Tianjin 300071, China.

ATP-binding cassette transporter A1 (ABCA1), a molecule mediating free cholesterol efflux from peripheral tissues to apoAI and high density lipoprotein (HDL), inhibits the formation of lipid-laden macrophage/foam cells and the development of atherosclerosis. ERK1/2 are important signaling molecules regulating cellular growth and differentiation. The ERK1/2 signaling pathway is implicated in cardiac development and hypertrophy. However, the role of ERK1/2 in the development of atherosclerosis, particularly in macrophage cholesterol homeostasis, is unknown. In this study, we investigated the effects of ERK1/2 activity on macrophage ABCA1 expression and cholesterol efflux. Compared with a minor effect by inhibition of other kinases, inhibition of ERK1/2 significantly increased macrophage cholesterol efflux to apoAI and HDL. In contrast, activation of ERK1/2 reduced macrophage cholesterol efflux and ABCA1 expression. The increased cholesterol efflux by ERK1/2 inhibitors was associated with the increased ABCA1 levels and the binding of apoAI to cells. The increased ABCA1 by ERK1/2 inhibitors was due to increased ABCA1 mRNA and protein stability. The induction of ABCA1 expression and cholesterol efflux by ERK1/2 inhibitors was concentration-dependent. The mechanism study indicated that activation of liver X receptor (LXR) had little effect on ERK1/2 expression and activation. ERK1/2 inhibitors had no effect on macrophage LXRalpha/beta expression, whereas they did not influence the activation or the inhibition of the ABCA1 promoter by LXR or sterol regulatory element-binding protein (SREBP). However, inhibition of ERK1/2 and activation of LXR synergistically induced macrophage cholesterol efflux and ABCA1 expression. Our data suggest that ERK1/2 activity can play an important role in macrophage cholesterol trafficking.
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http://dx.doi.org/10.1074/jbc.M109.073601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825427PMC
February 2010

Genetic deletion of low density lipoprotein receptor impairs sterol-induced mouse macrophage ABCA1 expression. A new SREBP1-dependent mechanism.

J Biol Chem 2008 Jan 20;283(4):2129-38. Epub 2007 Nov 20.

Center of Vascular Biology and Department of Pathology and Department of Medicine, Weill Cornell Medical College of Cornell University, New York, New York 10065, USA.

Low density lipoprotein receptor (LDLR) mutations cause familial hypercholesterolemia and early atherosclerosis. ABCA1 facilitates free cholesterol efflux from peripheral tissues. We investigated the effects of LDLR deletion (LDLR(-/-)) on ABCA1 expression. LDLR(-/-) macrophages had reduced basal levels of ABCA1, ABCG1, and cholesterol efflux. A high fat diet increased cholesterol in LDLR(-/-) macrophages but not wild type cells. A liver X receptor (LXR) agonist induced expression of ABCA1, ABCG1, and cholesterol efflux in both LDLR(-/-) and wild type macrophages, whereas expression of LXRalpha or LXRbeta was similar. Interestingly, oxidized LDL induced more ABCA1 in wild type macrophages than LDLR(-/-) cells. LDL induced ABCA1 expression in wild type cells but inhibited it in LDLR(-/-) macrophages in a concentration-dependent manner. However, lipoproteins regulated ABCG1 expression similarly in LDLR(-/-) and wild type macrophages. Cholesterol or oxysterols induced ABCA1 expression in wild type macrophages but had little or inhibitory effects on ABCA1 expression in LDLR(-/-) macrophages. Active sterol regulatory element-binding protein 1a (SREBP1a) inhibited ABCA1 promoter activity in an LXRE-dependent manner and decreased both macrophage ABCA1 expression and cholesterol efflux. Expression of ABCA1 in animal tissues was inversely correlated to active SREBP1. Oxysterols inactivated SREBP1 in wild type macrophages but not in LDLR(-/-) cells. Oxysterol synergized with nonsteroid LXR ligand induced ABCA1 expression in wild type macrophages but blocked induction in LDLR(-/-) cells. Taken together, our studies suggest that LDLR is critical in the regulation of cholesterol efflux and ABCA1 expression in macrophage. Lack of the LDLR impairs sterol-induced macrophage ABCA1 expression by a sterol regulatory element-binding protein 1-dependent mechanism that can result in reduced cholesterol efflux and lipid accumulation in macrophages under hypercholesterolemic conditions.
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http://dx.doi.org/10.1074/jbc.M706636200DOI Listing
January 2008

Functional interplay between the macrophage scavenger receptor class B type I and pitavastatin (NK-104).

Circulation 2004 Nov 22;110(22):3472-9. Epub 2004 Nov 22.

Center of Vascular Biology and Department of Pathology, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA.

Background: Scavenger receptor class B type I (SR-BI), a receptor for high-density lipoprotein (HDL), plays an important role in the bidirectional cholesterol exchange between cells and HDL particles and the atherosclerotic lesion development. Enhancement of SR-BI expression significantly reduces, whereas lack of SR-BI expression accelerates, the atherosclerotic lesion development in proatherogenic mice. Statins, a class of inhibitors for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, significantly suppress de novo cholesterol synthesis and reduce the incidence of coronary heart disease. Statins also display multiple pleiotropic effects independently of cholesterol synthesis in the vascular cells. Here, we investigated the effects of pitavastatin (NK-104), a newly synthesized statin, on macrophage SR-BI expression.

Methods And Results: We found that pitavastatin significantly increased SR-BI mRNA and protein expression in a macrophage cell line in a concentration- and time-dependent manner. It also increased SR-BI expression in both mouse peritoneal and human monocyte-derived macrophages. Associated with increased SR-BI expression, pitavastatin enhanced macrophage HDL binding, uptake of [14C]cholesteryl oleate/HDL, and efflux of [3H]cholesterol to HDL. Pitavastatin abolished the inhibition of macrophage SR-BI expression by cholesterol biosynthetic intermediates. It also restored SR-BI expression inhibited by lipopolysaccharide and tumor necrosis factor-alpha through its inactivation of the transcription factor nuclear factor-kappaB.

Conclusions: Our data demonstrate that pitavastatin can stimulate macrophage SR-BI expression by reduction of cholesterol biosynthetic intermediates and antiinflammatory action and suggest additional pleiotropic effects of statins by which they may reduce the incidence of coronary heart disease.
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http://dx.doi.org/10.1161/01.CIR.0000148368.79202.F1DOI Listing
November 2004

Pitavastatin downregulates expression of the macrophage type B scavenger receptor, CD36.

Circulation 2004 Feb;109(6):790-6

Center of Vascular Biology and Department of Pathology, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA.

Background: Pitavastatin (NK-104) is a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol biosynthesis. In clinical trials, pitavastatin has been shown to significantly decrease serum LDL cholesterol and triglyceride levels and increase HDL cholesterol. Scavenger receptor-mediated accumulation of oxidized LDL (OxLDL)-derived cholesteryl ester is considered to be a critical step in the development of atherosclerotic foam cell formation. We studied the effect of pitavastatin on CD36 (a class B scavenger receptor) expression by murine macrophages.

Methods And Results: Treatment of J774 cells and murine peritoneal macrophages with pitavastatin decreased CD36 mRNA expression in a dose-dependent manner. Decreased CD36 mRNA was associated with decreased CD36 cell surface protein expression in human THP-1 cells and human monocyte-derived macrophages. Pitavastatin also reduced the increase in CD36 mRNA, cell surface protein, and binding/uptake of OxLDL induced by peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands and/or OxLDL. Pitavastatin did not alter the half-life of CD36 mRNA, which suggests pitavastatin downregulates CD36 expression by reducing CD36 transcription. In addition, pitavastatin significantly decreased PPARgamma mRNA and protein expression. Finally, pitavastatin increased p44/42 mitogen-activated protein kinase activity and PPARgamma phosphorylation and increased the ratio of phosphorylated PPARgamma to nonphosphorylated PPARgamma.

Conclusions: The present data demonstrate that pitavastatin prevents OxLDL uptake by macrophages through PPARgamma-dependent inhibition of CD36 expression and suggest that pitavastatin could modulate CD36-mediated atherosclerotic foam cell formation.
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http://dx.doi.org/10.1161/01.CIR.0000112576.40815.13DOI Listing
February 2004

Regulation of peroxisome proliferator-activated receptor-gamma-mediated gene expression. A new mechanism of action for high density lipoprotein.

J Biol Chem 2002 Jun 12;277(26):23582-6. Epub 2002 Apr 12.

Center of Vascular Biology and Department of Pathology, Weill Medical College of Cornell University, New York, New York 10021, USA.

Cellular cholesterol content reflects a balance of lipid influx by lipoprotein receptors and endogenous synthesis and efflux to cholesterol acceptor particles. The beneficial effect of high density lipoprotein (HDL) in protecting against the development of cardiovascular disease is thought to be mediated predominately through its induction of cellular cholesterol efflux and "reverse cholesterol transport" from peripheral tissues to the liver. We tested the hypothesis that HDL could inhibit cellular lipid accumulation by modulating expression of peroxisome proliferator-activated receptor-gamma (PPARgamma)-responsive genes. To this end, we evaluated expression of two PPARgamma-responsive genes, CD36, a receptor for oxidized low density lipoprotein, and aP2, a fatty acid-binding protein. HDL decreased expression of macrophage CD36 and aP2 in a dose-dependent manner. HDL also decreased aP2 expression in fibroblasts, reduced accumulation of lipid, and slowed differentiation of fibroblasts into adipocytes. HDL stimulated mitogen-activated protein (MAP) kinase activity, and inhibition of CD36 expression was blocked by co-incubation with a MAP kinase inhibitor. HDL increased expression of PPARgamma mRNA and protein, induced translocation of PPARgamma from the cytoplasm to the nucleus, and increased PPARgamma phosphorylation. Our data demonstrate that despite induction and translocation of PPARgamma in response to HDL, MAP kinase-mediated phosphorylation of PPARgamma inhibited expression of PPARgamma-responsive genes and suggest mechanisms by which HDL may inhibit cellular lipid accumulation.
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http://dx.doi.org/10.1074/jbc.M200685200DOI Listing
June 2002
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