Naringenin inhibits TNF-α induced VSMC proliferation and migration via induction of HO-1
Naringenin inhibits TNF-α induced VSMC proliferation and migration via induction of HO-1
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DOI：
10.1016/j.fct.2012.06.006
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发表时间：
2012-09-01
影响因子：
4.3
通讯作者：
Liu, Chang
中科院分区：
文献类型：
--
作者：
Chen, Siyu;Ding, Yan;Liu, Chang
血管平滑肌细胞（VSMC）在各种炎症刺激下的增殖和迁移是动脉粥样硬化和再狭窄的重要发病机制。柚皮素是一种柑橘类黄酮，具有降脂和胰岛素样特性。在这里，我们研究了柚皮素是否影响TNF-α诱导的VSMC增殖和迁移，如果是这样，是否涉及血红素加氧酶-1（HO-1）。用单独的柚皮素或与TNF-α刺激的组合处理大鼠VSMC。我们发现，柚皮素诱导HO-1 mRNA和蛋白水平，以及其活性，在VSMCs。柚皮素以剂量依赖性方式抑制TNF-α诱导的VSMC增殖和迁移。机制研究表明，柚皮素抑制ERK/MAPK和Akt磷酸化，而不影响p38 MAPK和JNK。柚皮素还阻断了TNF-α诱导的ROS产生的增加。更重要的是，特异性HO-1抑制剂ZnPP IX或HO-1 siRNA部分消除了柚皮素对VSMCs的有益作用。这些结果表明，柚皮素可以作为一种新的药物，在这些病理治疗诱导HO-1的表达/活性，并随后降低VSMC增殖和迁移。(C)2012爱思唯尔有限公司保留所有权利。
Vascular smooth muscle cell (VSMC) proliferation and migration, which is triggered by various inflammatory stimuli, contributes importantly to the pathogenesis of atherosclerosis and restenosis. Naringenin is a citrus flavonoid with both lipid-lowering and insulin-like properties. Here, we investigated whether naringenin affects TNF-alpha-induced VSMC proliferation and migration and if so, whether heme oxygenase-1 (HO-1) is involved. Rat VSMCs were treated with naringenin alone or in combination of TNF-alpha stimulation. We found that naringenin induced HO-1 mRNA and protein levels, as well as its activity, in VSMCs. Naringenin inhibited TNF-alpha-induced VSMC proliferation and migration in a dose-dependent manner. Mechanistic study demonstrated that naringenin prevented ERK/MAPK and Akt phosphorylation while left p38 MAPK and JNK unchanged. Naringenin also blocked the increase of ROS generation induced by TNF-alpha. More importantly, the specific HO-1 inhibitor ZnPP IX or HO-1 siRNA partially abolished the beneficial effects of naringenin on VSMCs. These results suggest that naringenin may serve as a novel drug in the treatment of these pathologies by inducing HO-1 expression/activity and subsequently decreasing VSMC proliferation and migration. (C) 2012 Elsevier Ltd. All rights reserved.