A role for Snail-MnSOD axis in regulating epithelial-to-mesenchymal transition markers expression in RPE cells.
A role for Snail-MnSOD axis in regulating epithelial-to-mesenchymal transition markers expression in RPE cells.
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Snail-MnSOD 轴在调节 RPE 细胞上皮间质转化标志物表达中的作用。
DOI：
10.1016/j.bbrc.2021.11.039
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zhou Ti
中科院分区：
文献类型：
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作者：
Shen Gang;Li Yanmei;Hong Fuyan;Zhang Jing;Fang Zhenzhen;Xiang Wei;Qi Weiwei;Yang Xia;Gao Guoquan;Zhou Ti
视网膜相关性黄斑变性（AMD）是视力丧失的常见原因。视网膜色素上皮（RPE）细胞的上皮-间质转化（EMT），伴随着氧化损伤，在AMD中起着至关重要的作用。锰超氧化物歧化酶（MnSOD）由SOD 2编码，是抗氧化应激的关键分子，而Snail由SNAI 1编码，是EMT的关键转录因子。然而，MnSOD对RPE细胞EMT的影响及其机制尚不清楚。在这项研究中，我们发现MnSOD敲低通过上调Snail触发EMT，而MnSOD过表达逆转了RPE细胞中的EMT，即使用TGFβ处理，MnSOD的抗氧化应激活性介导了这一观察结果。此外，Snail缺失增加了MnSOD的表达和活性，而Snail过表达降低了MnSOD的表达和活性，双荧光素酶报告基因和ChIP测定显示Snail直接结合SOD 2启动子中的E-box（CACCTG）。MnSOD过表达和Snail干扰联合处理增强了细胞的抗氧化能力和EMT逆转作用。因此，我们的研究结果表明，MnSOD防止AMD的RPE细胞EMT通过抑制氧化损伤的RPE。此外，一个关键的EMT转录因子，蜗牛，作为一个新的负转录因子的SOD 2的功能。提示Snail-MnSOD轴在AMD的发生发展中形成了一个相互作用的环，这可能是预防AMD的一个新的系统治疗靶点。
Age-related macular degeneration (AMD) is a common cause of vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, accompanied by oxidative damage, plays a crucial role in AMD. It is well known that manganese superoxide dismutase (MnSOD) encoded by SOD2 is a critical molecule in fighting against oxidative stress, and Snail encoded by SNAI1 is the essential transcription factor for EMT. However, the effect of MnSOD on EMT and the underlying mechanism in RPE cells remains unknown. In this study, we found that MnSOD knockdown triggered the EMT by upregulating Snail, while MnSOD overexpression reversed EMT even with TGFβ treatment in RPE cells, and the anti-oxidative stress activity of MnSOD mediated this observation. In addition, Snail depletion increased both expression and activity of MnSOD while Snail overexpression decreased MnSOD expression and activity, and Dual-luciferase reporter and ChIP assays showed that Snail directly bound to E-box (CACCTG) in the SOD2 promoter. Moreover, MnSOD over-expression and Snail interference co-treatment strengthened the anti-oxidation and EMT reversing. Therefore, our findings demonstrate that MnSOD prevents EMT of RPE cells in AMD through inhibiting oxidative injury to RPE. Moreover, a critical EMT transcription factor, Snail, functions as a new negative transcriptional factor of SOD2. Herein, the Snail-MnSOD axis forms a mutual loop in the development of AMD, which may be a novel systemic treatment target for preventing AMD.