Ox-LDL Upregulates CRP Expression Through the IGF2 Pathway in THP-1 Macrophages
Ox-LDL Upregulates CRP Expression Through the IGF2 Pathway in THP-1 Macrophages
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Ox-LDL 通过 THP-1 巨噬细胞中的 IGF2 途径上调 CRP 表达
DOI：
10.1007/s10753-014-9964-4
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发表时间：
2015-04-01
期刊：
影响因子：
5.1
通讯作者：
Wang, Qian
中科院分区：
文献类型：
--
作者：
Li, Shu-Fen;Hu, Yan-Wei;Wang, Qian
c反应蛋白（CRP）是一种急性期反应蛋白，不仅在动脉粥样硬化发生风险中起预测作用，而且在动脉粥样硬化的发生和进展中也起着积极的作用。此外，越来越多的研究报道氧化低密度脂蛋白（Ox-LDL）在动脉粥样硬化的发生和发展中起着重要作用。然而，Ox-LDL对CRP表达的影响及其机制尚不清楚。分别用0、25、50、100 μg/mL的Ox-LDL或50 μg/mL的Ox-LDL处理THP-1巨噬细胞48小时，或分别用0、12、24、48小时。实时荧光定量PCR和Western blot检测各组mRNA和蛋白水平。我们发现Ox-LDL显著增加THP-1巨噬细胞中胰岛素样生长因子2 （IGF2）和CRP mRNA和蛋白水平，并呈剂量和时间依赖性。Ox-LDL增加了THP-1巨噬细胞中CRP蛋白的表达，而sirna介导的IGF2沉默完全消除了这种作用。此外，pcDNA3.1-IGF2治疗可显著提高ox - ldl刺激的THP-1巨噬细胞中CRP蛋白的表达。在THP-1巨噬细胞中，Ox-LDL通过IGF2途径上调CRP表达。
C-reactive protein (CRP) is an acute-phase reactant protein that not only plays a predictive role in determining atherogenesis risk but also represents an active participant in atherogenesis onset and progression. Moreover, an increasing number of studies have reported that oxidized low-density lipoprotein (Ox-LDL) plays a significant role in the initiation and progression of atherosclerosis. However, the effect and underlying mechanism of Ox-LDL on CRP expression remains unclear. THP-1 macrophages were treated with 0, 25, 50, or 100 μg/mL of Ox-LDL for 48 h, or 50 μg/mL of Ox-LDL for 0, 12, 24, and 48 h, respectively. Messenger RNA (mRNA) and protein levels were measured by real-time quantitative PCR and Western blot analysis, respectively. We found that Ox-LDL markedly increased insulin-like growth factor 2 (IGF2) and CRP mRNA and protein levels in a dose- and time-dependent manner in THP-1 macrophages. Treatment with Ox-LDL increased CRP protein expression, and this effect was completely abolished by siRNA-mediated silencing of IGF2 in THP-1 macrophages. Moreover, treatment with pcDNA3.1-IGF2 significantly enhanced CRP protein expression in Ox-LDL-stimulated THP-1 macrophages. CRP expression is upregulated by Ox-LDL through the IGF2 pathway in THP-1 macrophages.