EDEM1通过稳定ATF6促进颅内动脉瘤发展的作用研究

Role of EDEM1 in Promoting Intracranial Aneurysm Development by Stabilizing ATF6

目的:探究内质网降解增强α-甘露糖苷酶样蛋白1(EDEM1)和激活转录因子6(ATF6)在颅内动脉瘤(IA)发展中的作用。方法:纳入40例颅内动脉瘤患者和40例健康受试者,收集两组人群血清,通过ELISA检测ATF6水平。根据Hunt-Hess分级和Fisher分级将IA患者分为:轻度疾病组、中度疾病组和重度疾病组,比较3组患者血清中ATF6水平。将si-EDEM1和si-NC转染至HCAECs细胞,分组为si-EDEM1组和si-NC组,采用western blot检测两组细胞EDEM1和ATF6蛋白表达水平,CCK-8法检测两组细胞增殖水平。通过免疫共沉淀检测EDEM1和ATF6的相互作用情况。将si-ATF6和si-NC转染至HCAECs细胞,分组为si-ATF6组和si-NC组,采用Western blot检测两组细胞EDEM1和ATF6蛋白表达水平,CCK-8法检测两组细胞增殖水平。结果:与健康受试者相比,颅内动脉瘤患者血清中ATF6水平升高(P<0.05)。ATF6水平在轻度疾病组、中度疾病组和重度疾病组中依次递增(P<0.05)。与si-NC组相比,si-EDEM1组细胞EDEM1和ATF6蛋白表达水平降低,细胞增殖水平降低(P<0.05)。EDEM1和ATF6存在相互作用。与si-NC组相比,si-ATF6组细胞ATF6蛋白表达水平降低,细胞增殖水平降低(P<0.05)。结论:EDEM1通过稳定ATF6促进动脉内皮细胞增殖,与IA的恶化相关。

Objective:To investigate the role of endoplasmic reticulum-associated degradation-enhancingα-glucosidase-like protein 1(EDEM1)and activating transcription factor 6(ATF6)in the development of intracranial aneurysms(IA).Methods:Forty IA patients and 40 healthy subjects were recruited.Serum was collected from both groups,and ATF6 levels were detected by ELISA.IA patients were divided into mild,moderate,and severe disease groups according to Hunt-Hess and Fisher grading.ATF6 levels in the serum of the three groups were compared.si-EDEM1 and si-NC were transfected into HCAECs cells,and the cells were divided into si-EDEM1 and si-NC groups.Western blot was used to detect the expression levels of EDEM1 and ATF6 proteins in the two groups of cells,and CCK-8 assay was used to detect the proliferation of the two groups of cells.Co-immunoprecipitation was used to detect the interaction between EDEM1 and ATF6.si-ATF6 and si-NC were transfected into HCAECs cells,and the cells were divided into si-ATF6 and si-NC groups.Western blot was used to detect the expression levels of EDEM1 and ATF6 proteins in the two groups of cells,and CCK-8 assay was used to detect the proliferation of the two groups of cells.Results:Compared with healthy subjects,the serum ATF6 level in IA patients was increased(P<0.05).The ATF6 level increased sequentially in the mild,moderate,and severe disease groups(P<0.05).Compared with the si-NC group,the expression levels of EDEM1 and ATF6 proteins were decreased in the si-EDEM1 group cells,and the proliferation of the cells was decreased(P<0.05).EDEM1 and ATF6 interact with each other.Compared with the si-NC group,the expression level of ATF6 protein was decreased in the si-ATF6 group cells,and the proliferation of the cells was decreased(P<0.05).Conclusion:EDEM1 promotes the proliferation of arterial endothelial cells by stabilizing ATF6 and is associated with the progression of IA.