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HomeoboxC6 affects the apoptosis of human vascular endothelial cells and is involved in atherosclerosis.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-08-01 , DOI: 10.1002/jcp.29974 Xiangshu Long 1, 2, 3 , Ganhua You 2, 3 , Qiang Wu 2, 3 , Yu Zhou 1, 2 , Yan Xiao 2 , Fuxun Yu 4 , Shiyan Deng 2 , Rui Mo 2 , Fang Song 2 , Jing Huang 2 , Maobo Tian 2
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-08-01 , DOI: 10.1002/jcp.29974 Xiangshu Long 1, 2, 3 , Ganhua You 2, 3 , Qiang Wu 2, 3 , Yu Zhou 1, 2 , Yan Xiao 2 , Fuxun Yu 4 , Shiyan Deng 2 , Rui Mo 2 , Fang Song 2 , Jing Huang 2 , Maobo Tian 2
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Apoptosis of vascular endothelial cells (VECs) is highly important in the occurrence and development of atherosclerosis (AS). HomeboxC6 (HOXC6) is expressed in higher levels in multiple malignant tissues, and it influences the malignant biological behavior of the cancer cells. However, the effects of HOXC6 on AS and the apoptosis of VECs have not been fully elucidated. In this study, we demonstrated that HOXC6 expression was increased in aortic wall of AS rats and peripheral blood monocytes of patients with coronary heart disease. Furthermore, it was uncovered that BAX expression was upregulated, while BCL‐2 expression was downregulated in the aortic wall of AS rats. The apoptosis of human VECs (HVECs) cultured normally or treated with oxidized low‐density lipoprotein in vitro was decreased after transfection with HOXC6‐siRNA. Moreover, the results of Western blot analysis unveiled that the expressions of proapoptotic proteins, such as BAX, caspase‐3, cleaved‐caspase‐3, and caspase‐9 were reduced, while the expression of antiapoptotic protein, BCL‐2, was elevated. Meanwhile, mRNA and protein expressions of phospholipase C beta (PLCβ) were decreased, the phosphorylation levels of protein kinase C zeta (PKCζ) and nuclear transcription factor‐κB‐p65 (NF‐κBp65) and the membrane translocation of PKCζ were reduced as well. Besides, the expression of interleukin‐18 (IL‐18) protein was downregulated. However, after overexpression of HOXC6, the opposite trends of the abovementioned indices were observed. Furthermore, the inhibition of apoptosis induced by HOXC6‐siRNA was reversed by lysophosphatidylcholine, an activator of PKCζ. Taken together, our results indicated that HOXC6 can promote the apoptosis of HVECs and may be involved in the occurrence and development of AS, which may be partially associated with the activation of PLCβ/PKCζ/NF‐κBp65/IL‐18 signaling pathway.
中文翻译：
HomeoboxC6 影响人血管内皮细胞的凋亡并参与动脉粥样硬化。
血管内皮细胞（VEC）的凋亡在动脉粥样硬化（AS）的发生和发展中非常重要。 HomeboxC6（HOXC6）在多种恶性组织中高水平表达，影响癌细胞的恶性生物学行为。然而，HOXC6对AS和VEC凋亡的影响尚未完全阐明。在本研究中，我们证明 HOXC6 在 AS 大鼠主动脉壁和冠心病患者外周血单核细胞中表达增加。此外，还发现 AS 大鼠主动脉壁中 BAX 表达上调，而 BCL-2 表达下调。转染HOXC6 ‐siRNA后，正常培养或体外用氧化低密度脂蛋白处理的人VEC（HVEC）的凋亡减少。此外，Western blot分析结果显示，促凋亡蛋白，如BAX、caspase-3、cleaved-caspase-3和caspase-9的表达降低，而抗凋亡蛋白BCL-2的表达升高。 。同时，磷脂酶Cβ（PLCβ）的mRNA和蛋白表达降低，蛋白激酶Czeta（PKC z）和核转录因子-κB-p65（NF-κBp65）的磷酸化水平以及PKC z的膜转位也降低。此外，白介素-18（IL-18）蛋白的表达下调。然而，HOXC6过表达后，上述指标却出现了相反的趋势。此外， HOXC6 ‐siRNA 诱导的细胞凋亡抑制可被 PKC z 激活剂溶血磷脂酰胆碱逆转。 综上所述，我们的结果表明HOXC6可以促进HVECs凋亡，可能参与AS的发生和发展，这可能部分与PLCβ/PKCz/NF-κBp65/IL-18信号通路的激活有关。
更新日期：2020-08-01
中文翻译：
HomeoboxC6 影响人血管内皮细胞的凋亡并参与动脉粥样硬化。
血管内皮细胞（VEC）的凋亡在动脉粥样硬化（AS）的发生和发展中非常重要。 HomeboxC6（HOXC6）在多种恶性组织中高水平表达，影响癌细胞的恶性生物学行为。然而，HOXC6对AS和VEC凋亡的影响尚未完全阐明。在本研究中，我们证明 HOXC6 在 AS 大鼠主动脉壁和冠心病患者外周血单核细胞中表达增加。此外，还发现 AS 大鼠主动脉壁中 BAX 表达上调，而 BCL-2 表达下调。转染HOXC6 ‐siRNA后，正常培养或体外用氧化低密度脂蛋白处理的人VEC（HVEC）的凋亡减少。此外，Western blot分析结果显示，促凋亡蛋白，如BAX、caspase-3、cleaved-caspase-3和caspase-9的表达降低，而抗凋亡蛋白BCL-2的表达升高。 。同时，磷脂酶Cβ（PLCβ）的mRNA和蛋白表达降低，蛋白激酶Czeta（PKC z）和核转录因子-κB-p65（NF-κBp65）的磷酸化水平以及PKC z的膜转位也降低。此外，白介素-18（IL-18）蛋白的表达下调。然而，HOXC6过表达后，上述指标却出现了相反的趋势。此外， HOXC6 ‐siRNA 诱导的细胞凋亡抑制可被 PKC z 激活剂溶血磷脂酰胆碱逆转。 综上所述，我们的结果表明HOXC6可以促进HVECs凋亡，可能参与AS的发生和发展，这可能部分与PLCβ/PKCz/NF-κBp65/IL-18信号通路的激活有关。
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