Emodin Inhibits Homocysteine-Induced C-Reactive Protein Generation in Vascular Smooth Muscle Cells by Regulating PPARγ Expression and ROS-ERK1/2/p38 Signal Pathway.
Emodin Inhibits Homocysteine-Induced C-Reactive Protein Generation in Vascular Smooth Muscle Cells by Regulating PPARγ Expression and ROS-ERK1/2/p38 Signal Pathway.
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DOI：
10.1371/journal.pone.0131295
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Pang X;Liu J;Li Y;Zhao J;Zhang X
动脉粥样硬化是一种炎症性疾病。C-反应蛋白（CRP）作为一种炎症分子，在动脉粥样硬化的形成中起着直接的作用。血浆同型半胱氨酸（homocysteine，Hcy）水平升高是动脉粥样硬化的独立危险因素。我们以前报道过同型半胱氨酸通过诱导血管平滑肌细胞（VSMCs）中CRP的表达产生促炎作用。本研究观察大黄素对同型半胱氨酸诱导的大鼠血管平滑肌细胞CRP表达的影响及其分子机制。体外实验结果表明，大黄素预处理可抑制Hcy诱导的CRP mRNA和蛋白表达，且呈浓度依赖性。体内实验表明大黄素不仅在mRNA和蛋白水平上抑制血管壁CRP的表达，而且还降低了高同型半胱氨酸血症大鼠循环中CRP的水平。进一步研究表明大黄素可抑制Hcy诱导的VSMCs活性氧（ROS）的产生，减弱Hcy诱导的ERK 1/2和p38的磷酸化，上调Hcy抑制的过氧化物酶体增殖物激活受体γ（PPAR γ）的表达。表明大黄素能够抑制Hcy诱导的VSMCs CRP生成，其机制可能与干扰ROS-ERK 1/2/p38信号通路，上调PPAR γ表达有关。本研究为大黄素的抗炎和抗动脉粥样硬化作用提供了新的证据。
Atherosclerosis is an inflammatory disease. As an inflammatory molecule, C-reactive protein (CRP) plays a direct role in atherogenesis. It is known that the elevated plasma homocysteine (Hcy) level is an independent risk factor for atherosclerosis. We previously reported that Hcy produces a pro-inflammatory effect by inducing CRP expression in vascular smooth muscle cells (VSMCs). In the present study, we observed effect of emodin on Hcy-induced CRP expression in rat VSMCs and molecular mechanisms. The in vitro results showed that pretreatment of VSMCs with emodin inhibited Hcy-induced mRNA and protein expression of CRP in a concentration-dependent manner. The in vivo experiments displayed that emodin not only inhibited CRP expression in the vessel walls in mRNA and protein levels, but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further study revealed that emodin diminished Hcy-stimulated generation of reactive oxygen species (ROS), attenuated Hcy-activated phosphorylation of ERK1/2 and p38, and upregulated Hcy-inhibited expression of peroxisome proliferator-activated receptor gamma (PPARγ) in VSMCs. These demonstrate that emodin is able to inhibit Hcy-induced CRP generation in VSMCs, which is related to interfering with ROS-ERK1/2/p38 signal pathway and upregulating PPARγ expression. The present study provides new evidence for the anti-inflammatory and anti-atherosclerotic effects of emodin.
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