Antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal photoreceptor cells in a rat model of light-induced retinal injury.
Antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal photoreceptor cells in a rat model of light-induced retinal injury.
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DOI：
10.1016/j.biopha.2018.04.081
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发表时间：
2018-07
期刊：
影响因子：
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通讯作者：
Tian-zi Zhang;T. Hua;Limei Han;Yan Zhang;Guangsong Li;Qiuli Zhang;G. Su
中科院分区：
文献类型：
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作者：
Tian-zi Zhang;T. Hua;Limei Han;Yan Zhang;Guangsong Li;Qiuli Zhang;G. Su
目的：光损伤引起的视网膜感光细胞凋亡可导致视力丧失。这种损伤的机制尚不清楚，目前也没有有效的治疗方法。本研究的目的是在光致视网膜损伤大鼠模型中检测e1a刺激基因的细胞抑制因子（CREG）在视网膜细胞中的潜在抗凋亡作用。方法在视网膜轻度损伤大鼠玻璃体间隙注射screg蛋白。对照组玻璃体腔内注射等量PBS。1、3、7天后采集视网膜进行H&E染色和Western blotting分析。将P38、JNK和AKT的抑制剂或激动剂注入玻璃体以验证CREG的功能。结果在光致视网膜损伤大鼠中，CREG可抑制凋亡相关蛋白caspase-3、caspase-8、caspase-9以及磷酸化ERK （P-ERK）、磷酸化JNK （P-JNK）、磷酸化P38 （P-P38）、磷酸化AKT （P-AKT）信号蛋白的表达。PI3K-AKT抑制剂和P38和JNK激动剂可消除CREG对caspase-3表达的抑制作用。结论creg通过抑制P38/MAPK和JNK/MAPK信号通路，激活PI3K-AKT信号通路，保护视网膜细胞免于凋亡。
ObjectiveLight injury-induced apoptosis of retinal photoreceptor cells can lead to vision loss. The mechanism underlying such injury remains unclear, and there are no effective therapies at present. The aim of this study was to examine the potential antiapoptotic role of the cellular repressor of E1A-stimulated genes (CREG) in retinal cells in a rat model of light-induced retinal damage.MethodsCREG proteins were injected into the vitreous space of rats in which light retinal injury was induced. An equal volume of PBS was injected into the vitreous space of a control group. Retinas were collected for H&E staining and Western blotting analysis 1, 3, and 7 days later. Inhibitors or agonist for P38, JNK, and AKT were injected into the vitreous space to verify CREG function.ResultsIn rats with light-induced retinal injury, the CREG treatment inhibited the expression of apoptosis-related proteins caspase-3, caspase-8, and caspase-9 and signaling proteins phosphorylated ERK (P-ERK), phosphorylated JNK (P-JNK), phosphorylated P38 (P-P38), and phosphorylated AKT (P-AKT). An inhibitor of PI3K-AKT and an agonists of P38 and JNK abrogated the inhibitory effect of CREG on caspase-3 expression.ConclusionCREG protected retinal cells against apoptosis by inhibiting P38/MAPK and JNK/MAPK signaling pathways and activating the PI3K-AKT signaling pathway.