E3 ubiquitin ligase CBL-B suppresses vascular endothelial cell pyroptosis and injury in intracranial aneurysm by facilitating NLRP3 degradation  

作　　者：WEI ZHENG CHENG LIU 

机构地区：[1]Department of Neurosurgery,Jingzhou Hospital of Traditional Chinese Medicine,Jingzhou,434000,China [2]Department of Critical Care Medicine,Jingzhou Hospital of Traditional Chinese Medicine,Jingzhou,434000,China

出　　处：《BIOCELL》2024年第2期293-301,共9页生物细胞(英文)

摘　　要：Objective:Intracranial aneurysm(IA)represents a devastating disease with high rates of disability and mortality,which is initiated by dysfunction of endothelial cells(ECs).Evidence suggests the dysregulation of the E3 ubiquitin ligase family during EC injury.In this work,the role of an E3 ubiquitin ligase,casitas B lymphoma-B(CBLB),was explored in human brain microvascular EC(HBMEC)function through the NLRP3 pathway.Methods:In vitro IA model was induced by treating HBMECs with oxidized low-density lipoprotein(ox-LDL).The levels of CBLB and pyroptosis-related proteins NLRP3,ASC,cleaved caspase-1,and GSDME-N were determined by real-timequantitative polymerase chain reaction and western blotting.HBMEC apoptosis,proliferation,and migration were evaluated by flow cytometry,MTT,and scratch tests.An enzyme-linked immunosorbent assay was conducted to measure interleukin(IL)-1βand IL-18 levels in cell culture supernatant.The ubiquitination of NLRP3 was detected by co-immunoprecipitation.Results:NLRP3 was highly expressed while CBL-B was weakly expressed in ox-LDL-treated HBMECs.Cell apoptosis was enhanced,proliferation and migration were weakened,NLRP3 inflammasome was activated,and levels of gasdermin E-N,IL-1β,and IL-18 were increased in ox-LDL-induced HBMECs.The above tendencies were counteracted by NLRP3 knockdown or CBL-B overexpression.Additionally,CBL-B overexpression increased NLRP3 ubiquitination,suggesting that CBL-B hampered the activation of NLRP3 inflammasome by ubiquitinating NLRP3.Conclusion:E3 ubiquitin ligase CBL-B accelerates NLRP3 degradation to impede HBMEC pyroptosis,thus palliating vascular EC injury in IA.

关 键 词：CBL-B NLRP3 Vascular endothelial cell Intracranial aneurysm Cell pyroptosis 

分 类 号：R73[医药卫生—肿瘤]