Propranolol induces apoptosis of human umbilical vein endothelial cells through downregulation of CD147
Propranolol induces apoptosis of human umbilical vein endothelial cells through downregulation of CD147
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DOI：
10.1111/bjd.12193
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发表时间：
2013-04-01
影响因子：
10.3
通讯作者：
Chen, X.
中科院分区：
文献类型：
--
作者：
Xie, W.;Xie, H.;Chen, X.
背景：婴儿血管瘤（IHs）是婴儿期的良性肿瘤。大多数IHs患者不需要治疗。然而，如果有明显的审美或功能损害，则需要治疗。目前治疗复杂IHs最有希望的方法是口服心得安，但其作用机制尚不清楚。目的探讨CD147在普萘洛尔诱导的人脐静脉内皮细胞（HUVECs）凋亡中的作用。方法应用心得安治疗人脐静脉内皮细胞，采用以下方法观察其治疗效果。(i)采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）法和流式细胞术检测细胞增殖和凋亡。（ii）采用逆转录聚合酶链反应和Western blotting检测CD147的表达水平。（iii）用编码CD147短发夹（sh） RNA或CD147 cDNA的慢病毒转染HUVECs。用MTT法和流式细胞术检测转染后细胞增殖和凋亡的变化。（iv）应用Western blotting检测经心得安治疗和/或转染CD147 shRNA后HUVECs中bcl -2相关死亡启动子（BAD） Ser112位点磷酸化水平。结果心得安抑制huvec细胞增殖，诱导细胞凋亡。它以浓度依赖性的方式降低CD147蛋白的表达。敲低CD147不仅能诱导细胞凋亡，还能加重心得安引发的huvec细胞凋亡。过表达CD147可保护huvec细胞凋亡和心得安诱导的细胞凋亡。此外，普萘洛尔和CD147的下调均可下调BAD的Ser112磷酸化，表明普萘洛尔和CD147通过相同的信号转导途径诱导huvec细胞凋亡。结论普萘洛尔诱导的HUVECs细胞凋亡可能通过下调CD147介导。这项研究强调了心得安作用的新步骤，并提出了治疗IHs的潜在新靶点。
Background Infantile haemangiomas (IHs) are benign tumours in infancy. Most patients suffering from IHs do not require treatment. However, if there is a dramatic aesthetic or functional impairment, treatment is needed. Currently the most promising therapy for complicated IHs is the oral administration of propranolol, but its mechanism is unclear.Objectives To investigate the role of CD147 in propranolol-induced apoptosis in human umbilical vein endothelial cells (HUVECs).Methods Human umbilical vein endothelial cells were treated with propranolol, and the treatment effects were investigated through the following methodology. (i) Cell proliferation and apoptosis were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis. (ii) The expression level of CD147 was measured by reverse-transcription polymerase chain reaction and Western blotting. (iii) HUVECs were transfected with lentivirus encoding CD147 short hairpin (sh) RNA or CD147 cDNA. Ensuing changes in cell proliferation and apoptosis after transfection were measured using the MTT assay and flow cytometry. (iv) The level of phosphorylation of Bcl-2-associated death promoter (BAD) at Ser112 in HUVECs after propranolol treatment and/or CD147 shRNA transfection was detected by Western blotting.Results Propranolol inhibited cell proliferation and induced apoptosis in HUVECs. It decreased CD147 protein expression in a concentration-dependent manner. Knocking down CD147 not only induced apoptosis but also exacerbated the apoptosis triggered by propranolol in HUVECs. Overexpression of CD147 can protect HUVECs from apoptosis and propranolol-induced apoptosis. Furthermore, knockdown of both propranolol and CD147 can downregulate Ser112 phosphorylation of BAD, indicating that propranolol and CD147 induce apoptosis in HUVECs through the same signalling transduction pathway.Conclusions Our studies demonstrate that propranolol-induced apoptosis may be mediated through the downregulation of CD147 in HUVECs. This study highlights a novel step in propranolol action and suggests a potential new target for the treatment of IHs.