EDEM1通过稳定ATF6促进颅内动脉瘤发展的作用  

Role of EDEM1 stabilizing ATF6 in the development of intracranial aneurysms

作　　者：张信 梁文宝[1] 赵恒[1] 芦晨宇 刘新志[1] Zhang Xin;Liang Wenbao;Zhao Heng;Lu Chenyu;Liu Xinzhi(Third Department of Surgery,Fourth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第四附属医院外三科,乌鲁木齐830000

出　　处：《脑与神经疾病杂志》2024年第9期529-534,共6页Journal of Brain and Nervous Diseases

基　　金：新疆维吾尔自治区自然科学基金资助项目(2020D01C141)。

摘　　要：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IA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,IA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疾病恶化相关。Objective To investigate the roles of endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 1(EDEM1)and activating transcription factor 6(ATF6)in the development of intracranial aneurysms(IA).Methods Forty patients with IA and forty healthy subjects were enrolled.Serum samples were collected from both groups,and ATF6 levels were measured using ELISA.Based on Hunt-Hess and Fisher grading,patients were categorized into mild,moderate,and severe disease groups,and serum ATF6 levels were compared among these groups.HCAECs cells were transfected with si-EDEM1 and si-NC,resulting in si-EDEM1 and si-NC groups.Western blot was used to assess protein expression levels of EDEM1 and ATF6 in these groups,along with CCK-8 assay to evaluate cell proliferation.Immunoprecipitation was performed to examine the interaction between EDEM 1 and ATF6.Similarly,si-ATF6 and si-NC were transfected into HCAECs cells,and protein expression levels of EDEM 1 and ATF6 were measured using Western blot,with cell proliferation assessed using CCK-8 assay.Results Serum ATF6 levels were elevated in patients with IA compared to healthy subjects(P<0.05).ATF6 levels increased progressively in the mild,moderate,and severe disease groups(P<0.05).In the si-EDEM1 group,protein expression levels of EDEM1 and ATF6 were reduced,leading to decreased cell proliferation compared to the si-NC group(P<0.05).EDEM1 and ATF6 were found to interact with each other.In the si-ATF6 group,ATF6 protein expression levels decreased,accompanied by decreased cell proliferation compared to the si-NC group(P<0.05).Conclusion EDEM1 enhances endothelial cell proliferation by stabilizing ATF6,contributing to the progression of IA.

关 键 词：颅内动脉瘤 动脉内皮细胞 内质网降解增强α-甘露糖苷酶样蛋白1 激活转录因子6 

分 类 号：R651[医药卫生—外科学]