Department of Medicine, Jinan Maternity and Child Care Hospital, Jinan, Shandong, China.
J Biochem Mol Toxicol. 2023 Oct;37(10):e23439. doi: 10.1002/jbt.23439. Epub 2023 Jul 31.
Abnormal apoptosis of vascular endothelial cells is an important feature of arteriosclerosis (AS). Here, we induced apoptosis in human umbilical vein endothelial cells (HUVECs) using transforming growth factor-β (TGF-β), and investigated the role of antiapoptotic E3 ubiquitin ligase (AREL1) in the apoptosis of vascular endothelial cells. We proved that AREL1 is downregulated in TGF-β treated HUVECs. The overexpression of AREL1 inhibits the activation of Caspase-3 and Caspase-9 and attenuates cell apoptosis induced by TGF-β. According to the result of coimmunoprecipitation, AREL1 interacts with the proapoptotic proteins the second mitochondria-derived activator of caspases (SMAC) in TGF-β treated HUVECs. In addition, miR-320b inhibits the expression of AREL1, and the overexpression of AREL1 attenuates the apoptosis induced by miR-320b mimics in HUVECs. In conclusion, AREL1 is downregulated by miR-320b. AREL1 overexpression inhibits TGF-β induced apoptosis through downregulating SMAC in vascular endothelial cells. Our study explores pathogenesis regulation mechanism and new biological therapeutic targets for vascular disease.
血管内皮细胞的异常凋亡是动脉粥样硬化（AS）的一个重要特征。在这里，我们用转化生长因子-β（TGF-β）诱导人脐静脉内皮细胞（HUVEC）凋亡，并研究了抗凋亡 E3 泛素连接酶（AREL1）在血管内皮细胞凋亡中的作用。我们证明，AREL1 在 TGF-β 处理的 HUVEC 中下调。AREL1 的过表达抑制了 Caspase-3 和 Caspase-9 的激活，并减轻了 TGF-β 诱导的细胞凋亡。根据共免疫沉淀的结果，AREL1 与促凋亡蛋白第二线粒体衍生的半胱天冬酶激活剂（SMAC）在 TGF-β 处理的 HUVEC 中相互作用。此外，miR-320b 抑制 AREL1 的表达，而 AREL1 的过表达减轻了 miR-320b 模拟物在 HUVEC 中诱导的凋亡。总之，miR-320b 下调 AREL1 的表达。AREL1 的过表达通过下调血管内皮细胞中的 SMAC 抑制 TGF-β 诱导的凋亡。我们的研究探索了血管疾病的发病机制调控机制和新的生物治疗靶点。
