Role of EDEM1 in Promoting Intracranial Aneurysm Development by Stabilizing ATF6
Objective:To investigate the role of endoplasmic reticulum-associated degradation-enhan-cing α-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 prolifera-tion of arterial endothelial cells by stabilizing ATF6 and is associated with the progression of IA.
Intracranial aneurysmEndoplasmic reticulum-associated degradation-enhancing α-glucosidase-like protein 1Activating transcription factor 6
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