Induction of DKK1 by ox-LDL negatively regulates intracellular lipid accumulation in macrophages
Induction of DKK1 by ox-LDL negatively regulates intracellular lipid accumulation in macrophages
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ox-LDL 诱导 DKK1 负向调节巨噬细胞细胞内脂质积累
DOI：
10.1016/j.febslet.2014.11.023
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发表时间：
2015-01-02
期刊：
影响因子：
3.5
通讯作者：
Zhang, Mei
中科院分区：
文献类型：
--
作者：
Zhang, Yu;Ge, Cheng;Zhang, Mei
Dickkopf 1（DKK 1）是一种经典的Wnt/β-catenin通路拮抗剂，与心血管疾病和脂肪形成密切相关。我们进行了一项体外研究，以确定氧化低密度脂蛋白（ox-LDL）是否增加巨噬细胞中DKK 1的表达，以及β-连环蛋白和肝脏X受体α（LXR α）是否参与了这种调节。ox-LDL诱导DKK 1表达通过Wnt/β-catenin途径降低凝集素样氧化低密度脂蛋白受体-1（LOX-1）水平，通过信号转导和转录激活因子3（STAT 3）途径增加ATP结合盒转运蛋白A/G1（ABCA/G1）水平。较低的LOX-1和较高的ABCA/G1水平抑制巨噬细胞中的胆固醇负荷。总之，ox-LDL可能通过下调LOX-1介导的脂质摄取和上调ABCA/G1依赖性胆固醇流出的机制诱导巨噬细胞中DKK 1表达以抑制脂质蓄积。(C)2014年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
Dickkopf1 (DKK1), a canonical Wnt/beta-catenin pathway antagonist, is closely associated with cardiovascular disease and adipogenesis. We performed an in vitro study to determine whether oxidized low-density lipoprotein (ox-LDL) increased the expression of DKK1 in macrophages and whether beta-catenin and liver X receptor alpha (LXR alpha) were involved in this regulation. Induction of DKK1 expression by ox-LDL decreased the level of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) via a Wnt/beta-catenin pathway and increased ATP-binding cassette transporter A/G1 (ABCA/G1) levels via a signal transducer and activator of transcription 3 (STAT3) pathway. Lower LOX-1 and higher ABCA/G1 levels inhibited cholesterol loading in macrophages. In conclusion, ox-LDL may induce DKK1 expression in macrophages to inhibit the accumulation of lipids through a mechanism that involves downregulation of LOX-1-mediated lipid uptake and upregulation of ABCA/G1-dependent cholesterol efflux. (C) 2014 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.