Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways
Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways
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Apelin 通过 APJ/PI3-K/Akt 信号通路抑制人血管平滑肌细胞凋亡
DOI：
10.1007/s00726-010-0555-x
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发表时间：
2010-11-01
期刊：
影响因子：
3.5
通讯作者：
Liao, Er-Yuan
中科院分区：
文献类型：
--
作者：
Cui, Rong-Rong;Mao, Ding-An;Liao, Er-Yuan
血管平滑肌细胞(VSMCs)的凋亡在心血管疾病中调节血管重塑中起着重要作用。Apelin是G蛋白偶联受体APJ的内源性配体，在心血管系统中发挥重要作用。然而，apelin对VSMCs凋亡的作用机制尚不清楚。以培养的人血管平滑肌细胞作为研究细胞凋亡的模型，探讨apelin与人血管平滑肌细胞凋亡的关系及其信号转导途径。通过Western blotting，我们证实VSMC能够表达APJ。为了评价apelin在VSMC凋亡中的可能作用，我们研究了apelin对人VSMCs凋亡的影响。结果表明，Apelin可抑制血清剥夺诱导的人VSMCs的凋亡。用小干扰RNA(SiRNA)抑制APJ可阻断Apelin的抗凋亡活性。Apelin可增加Bcl2蛋白表达，降低Bax蛋白表达。Apelin刺激后，细胞外信号调节蛋白激酶(ERK)和磷脂酰肌醇3-激酶下游效应蛋白Akt的活性增加。用siRNA抑制APJ可阻断Apelin诱导的ERK和Akt的激活。PI3-K抑制剂LY294002可阻断Apelin诱导的Akt激活，并取消Apelin诱导的抗凋亡活性。我们的研究表明，Apelin抑制血清剥夺诱导的人VSMCs的凋亡，其抗凋亡作用是通过APJ/PI3-K/Akt信号通路介导的。
Apoptosis of vascular smooth muscle cells (VSMCs) plays an important role in regulating vascular remodeling during cardiovascular diseases. Apelin is the endogenous ligand for the G-protein-coupled receptor APJ and plays an important role in the cardiovascular system. However, the mechanisms of apelin on apoptosis of VSMCs have not been elucidated. Using a culture of human VSMCs as a model for the study of apoptosis, the relationship between apelin and apoptosis of human VSMCs and the signal pathway involved were investigated. Using western blotting, we confirmed that VSMCs could express APJ. To evaluate the possible role of apelin in VSMC apoptosis, we assessed its effect on apoptosis of human VSMCs. The results showed that apelin inhibited human VSMCs apoptosis induced by serum deprivation. Suppression of APJ with small-interfering RNA (siRNA) abolished the anti-apoptotic activity of apelin. Apelin increased Bcl-2 protein expression, but decreased Bax protein expression. An increase in activation of extracellular signal-regulated protein kinase (ERK) and Akt (a downstream effector of phosphatidylinositol 3-kinase) was shown after apelin stimulation. Suppression of APJ with siRNA abolished the apelin-induced activation of ERK and Akt. LY294002 (a PI3-K inhibitor) blocked apelin-induced activation of Akt and abolished the apelin-induced antiapoptotic activity. Our study suggests that apelin suppresses serum deprivation-induced apoptosis of human VSMCs, and that the anti-apoptotic action is mediated through the APJ/PI3-K/Akt signaling pathways.