NOX4-Derived Reactive Oxygen Species Drive Apelin-13-Induced Vascular Smooth Muscle Cell Proliferation via the ERK Pathway
NOX4-Derived Reactive Oxygen Species Drive Apelin-13-Induced Vascular Smooth Muscle Cell Proliferation via the ERK Pathway
复制标题
NOX4 衍生的活性氧通过 ERK 途径驱动 Apelin-13 诱导的血管平滑肌细胞增殖
DOI：
10.1007/s10989-011-9269-5
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发表时间：
2011-12-01
影响因子：
2.5
通讯作者：
Li, Jian
中科院分区：
文献类型：
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作者：
Li, Lanfang;Li, Fang;Li, Jian
Apelin 是 G 蛋白偶联受体 apelin-血管紧张素受体样 1 (APJ) 的内源性配体。血管平滑肌细胞表达apelin和APJ，它们是心血管系统中的重要调节因子。 Apelin-13 显着刺激血管平滑肌细胞增殖。然而，对于 apelin-13 诱导血管平滑肌细胞增殖的精确细胞机制知之甚少。在这里，我们提出的新数据表明 NADPH 氧化酶 4 衍生的活性氧在用 apelin-13 处理的血管平滑肌细胞增殖中的关键作用。 Apelin-13 以浓度和时间依赖性方式刺激活性氧的产生。此外，DPI 还会损害 apelin-13 诱导的活性氧生成和血管平滑肌细胞增殖。 Apelin-13 处理以剂量依赖性方式增加 NADPH 氧化酶 4 的表达。使用 siRNA 下调 NADPH 氧化酶 4 可阻止 apelin-13 诱导的活性氧生成和血管平滑肌细胞增殖。反应分子的增加可以触发 ERK 应激敏感信号通路的激活。此外，siRNA-NOX4 和 DPI 逆转了 apelin-13 诱导的 ERK 磷酸化。 Apelin-13 通过 ERK 信号通路通过 NOX4 衍生的 ROS 诱导血管平滑肌细胞增殖。
Apelin is the endogenous ligand of the G-protein-coupled receptor, apelin-angiotensin receptor-like 1 (APJ). Vascular smooth muscle cells express both apelin and APJ, which are important regulatory factors in the cardiovascular system. Apelin-13 significantly stimulated vascular smooth muscle cell proliferation. However, little is known about the precise cellular mechanisms responsible for vascular smooth muscle cell proliferation induced by apelin-13. Here, we present novel data that indicate the key role of NADPH oxidase 4-derived reactive oxygen species in proliferation of vascular smooth muscle cells treated with apelin-13. Apelin-13 stimulated reactive oxygen species production in a concentration-and time-dependent manner. Furthermore, DPI impaired apelin-13-induced reactive oxygen species generation and vascular smooth muscle cell proliferation. Apelin-13-treatment increased the expression of NADPH oxidase 4 in a dose-dependent manner. Down-regulation of NADPH oxidase 4 using siRNA prevented apelin-13-induced reactive oxygen species generation and vascular smooth muscle cell proliferation. An increase in reactive molecules can trigger the activation of ERK stress-sensitive signaling pathways. Additionally, siRNA-NOX4 and DPI reversed the phosphorylation of ERK induced by apelin-13. Apelin-13 induced vascular smooth muscle cell proliferation by NOX4-derived ROS via the ERK signaling pathway.