摘要
背景:前期研究显示,E1A激活基因阻遏子能够通过抑制动脉平滑肌细胞的凋亡对抗动脉粥样硬化。目的:进一步阐明E1A激活基因阻遏子在内皮细胞凋亡中的作用。方法:通过去血清方法诱导体外培养的人脐静脉内皮细胞凋亡,然后进行TUNEL和caspase-3的活性检测。结果与结论:伴随着E1A激活基因阻遏子的表达下降,内皮细胞的凋亡增多。功能获得和功能缺失分析显示:E1A激活基因阻遏子过表达后能够明显抑制内皮细胞的凋亡,而E1A激活基因阻遏子表达减少可以明显增加诱导内皮细胞的凋亡。进一步应用Western blot分析显示:E1A激活基因阻遏子对于内皮细胞凋亡的保护作用主要通过激活PI3K/AKT信号通路介导。提示E1A激活基因阻遏子对抗去血清诱导的内皮细胞凋亡中具有重要的作用。并且,E1A激活基因阻遏子抑制的内皮细胞凋亡可能通过PI3K/AKT信号转导通路。
BACKGROUND：Previous studies have demonstrated that there is a protective effect of cellular repressor of E1A-stimulated genes（CREG） against atherosclerosis through prevention of vascular smooth muscle cell apoptosis.However,the role of CREG in endothelial cells（ECs） apoptosis and its underlying signal mechanism is unknown.OBJECTIVE：To further illustrate the effect of CREG on the apoptosis of ECs.METHODS：The apoptosis of human umbilical vein endothelial cells（HUVECs） was induced by serum deprived culture,as well as the expression of CREG was detected by Western blot.TUNEL staining and caspase-3 activity assays were used to evaluate the apoptosis of HUVECS.Furthermore,gain-and loss-of-function analysis was used to reveal the bio-function of CREG in HUVEC apoptosis.RESULTS AND CONCLUSION：Western blot revealed that the apoptosis of ECs was increased with the decreasing of CREG expression.Moreover,gain-and loss-of-function identified that CREG could significantly inhibit ECs apoptosis after the overexpression,whereas the decrease of CREG overexpression could obviously increased and induced.Meanwhile,Western analysis demonstrated that the protective effect of CREG on ECs apoptosis might mainly mediated by activating PI3K/AKT signaling serum starvation pathway.These results suggest that CREG plays a critical role in protecting the vascular endothelium from apoptosis,and the protective effect of CREG against ECs apoptosis may be related with the transduction of PI3K/AKT signaling pathway.
出处
《中国组织工程研究》
CAS
CSCD
2012年第46期8693-8697,共5页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金资助项目(81070097
30971218)
辽宁省科技攻关项目(200925009-9)
辽宁省自然科学基金(20092088
20092090)~~
