17β-Oestradiol Attenuates the Photoreceptor Apoptosis in Mice with Retinitis Pigmentosa by Regulating N-myc Downstream Regulated Gene 2 Expression
17β-Oestradiol Attenuates the Photoreceptor Apoptosis in Mice with Retinitis Pigmentosa by Regulating N-myc Downstream Regulated Gene 2 Expression
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17β-雌二醇通过调节 N-myc 下游调节基因 2 表达来减弱视网膜色素变性小鼠的感光细胞凋亡
DOI：
10.1016/j.neuroscience.2020.11.010
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发表时间：
2020-11
期刊：
影响因子：
3.3
通讯作者：
Xiao-Rui Yu（通讯作者）
中科院分区：
文献类型：
--
作者：
Ye-Cheng Xiong;Tao Chen;Xiao-Bei Yang;Chun-Lei Deng;Qi-Lan Ning;Rui Quan;Xiao-Rui Yu（通讯作者）
视网膜色素变性（RP）是一组异质性的视网膜变性疾病，其最终病理特征是感光细胞凋亡。目前，RP的发病机制仍然知之甚少，治疗无效。17β-雌二醇（βE2）是公认的神经退行性疾病中的神经保护因子，并且在光诱导的视网膜变性模型中表现出神经保护作用。最近，我们确定了N-myc下游调节基因2（NDRG 2）的抑制作为小鼠视网膜光感受器特异性细胞死亡的分子标志物。据报道，βE2还可调节唾液腺泡细胞中的NDRG 2。因此，在本研究中，我们研究了βE2是否在RP中起保护作用并调节感光细胞中的NDRG 2。为此，我们建立了RP模型，并观察到βE2不仅减少了RP模型中感光细胞的凋亡，而且恢复了NDRG 2的表达水平。然后，我们在细胞RP模型中显示siNDRG 2抑制βE2对感光细胞的抗凋亡作用。随后，我们使用经典的雌激素受体（ER）拮抗剂减弱βE2的作用，表明βE2通过经典的ER发挥作用。此外，我们还对该基因进行了生物信息学分析，结果表明，已报道的雌激素反应元件（ERE）序列存在于小鼠NDRG 2基因的启动子区。总之，我们的研究结果表明，βE2通过经典的ER介导的机制维持NDRG 2的表达来减弱RP模型中感光细胞的凋亡。
Retinitis pigmentosa (RP) is a heterogeneous group of retinal degenerative diseases in which the final pathological feature is photoreceptor cell apoptosis. Currently, the pathogenesis of RP remains poorly understood and therapeutics are ineffective. 17β-Oestradiol (βE2) is universally acknowledged as a neuroprotective factor in neurodegenerative diseases and has manifested neuroprotective effects in a light-induced retinal degeneration model. Recently, we identified N-myc downstream regulated gene 2 (NDRG2) suppression as a molecular marker of mouse retinal photoreceptor-specific cell death. βE2 has also been reported to regulate NDRG2 in salivary acinar cells. Therefore, in this study, we investigated whether βE2 plays a protective role in RP and regulates NDRG2 in photoreceptor cells. To this end, we generated RP models and observed that βE2 not only reduced the apoptosis of photoreceptor cells, but also restored the level of NDRG2 expression in RP models. Then, we showed that siNDRG2 inhibits the anti-apoptotic effect of βE2 on photoreceptor cells in a cellular RP model. Subsequently, we used a classic oestrogen receptor (ER) antagonist to attenuate the effects of βE2, suggesting that βE2 exerted its effects on RP models via the classic ERs. In addition, we performed a bioinformatics analysis, and the results indicated that the reported oestrogen response element (ERE) sequence is present in the promoter region of the mouseNDRG2gene. Overall, our results suggest that βE2 attenuated the apoptosis of photoreceptor cells in RP models by maintaining NDRG2 expression via a classic ER-mediated mechanism.
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影响因子：
--
作者：
C. Sippl;E. Tamm
通讯作者：
C. Sippl;E. Tamm
影响因子：
3.7
作者：
Ding F;Yao J;Zhao L;Mao Z;Chen S;Brinton RD
通讯作者：
Brinton RD
影响因子：
1.1
作者：
N. R. Miller;T. Jover;Hillel W. Cohen;R. Zukin;A. M. Etgen
通讯作者：
N. R. Miller;T. Jover;Hillel W. Cohen;R. Zukin;A. M. Etgen
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影响因子：
4.1
作者：
Tang H;Zhang Q;Yang L;Dong Y;Khan M;Yang F;Brann DW;Wang R
通讯作者：
Wang R
影响因子：
6.2
作者：
S. L. Roche;Ana M. Ruiz-Lopez;Jennifer N. Moloney;A. Byrne;T. Cotter
通讯作者：
S. L. Roche;Ana M. Ruiz-Lopez;Jennifer N. Moloney;A. Byrne;T. Cotter