ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells.
ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells.
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ERK 和 Akt 信号通路参与大鼠血管平滑肌细胞晚期糖基化终产物诱导的自噬
DOI：
10.3892/ijmm.2012.891
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发表时间：
2012-04
影响因子：
5.4
通讯作者：
He H
中科院分区：
文献类型：
--
作者：
Hu P;Lai D;Lu P;Gao J;He H
晚期糖基化终产物(AGEs)在糖尿病患者血管平滑肌细胞(VSMCs)增殖和加速动脉粥样硬化中起重要作用。自噬是一种维持生命的过程，在动脉粥样硬化斑块中受到氧化脂质、炎症和代谢应激条件的刺激。在我们的研究中，我们使用了四甲基偶氮唑盐比色法来证明自噬参与了年龄诱导的血管平滑肌细胞的增殖。此外，AGEs(100μg/ml)可诱导大鼠主动脉VSMC的自噬，并呈时间和剂量依赖性。这些结果得到了电子显微镜和免疫荧光成像的进一步证实。AGEs可激活ERK、JNK和p38/MAPK，但抑制Akt。ERK抑制剂和Akt激活剂可抑制AGE诱导的自噬，表明AGEs通过ERK和Akt信号通路诱导VSMC自噬。此外，RAGE的RNA干扰减少了自噬，表明RAGE在AGE诱导的自噬过程中起着关键作用。因此，AGE诱导的自噬参与了AGE诱导的VSMCs增殖过程，这与糖尿病的动脉粥样硬化有关。
Advanced glycation end products (AGEs) play an important role in the proliferation of vascular smooth muscle cells (VSMCs) and accelerate atherosclerosis in diabetic patients. Autophagy, a life-sustaining process, is stimulated in atherosclerotic plaques by oxidized lipids, inflammation and metabolic stress conditions. In our studies, we utilized MTT assays to show that autophagy is involved in AGE-induced proliferation of VSMCs. Furthermore, treatment with AGEs (100 μg/ml) could induce autophagy in a time- and dose-dependent manner in rat aortic VSMCs. These results were further substantiated by electron microscopy and immunofluorescence imaging. Treatment with AGEs activated ERK, JNK and p38/MAPK, but inhibited Akt. Pretreatment with an ERK inhibitor and an Akt activator inhibited AGE-induced autophagy, demonstrating that AGEs induce autophagy in VSMCs through the ERK and Akt signaling pathways. In addition, RNA interference of RAGE decreased autophagy, indicating that RAGE is pivotal in the process of AGE-induced autophagy. Therefore, AGE-induced autophagy contributes to the process of AGE-induced proliferation of VSMCs, which is related to atherosclerosis in diabetes.
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影响因子：
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通讯作者：
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