NFE2/miR-423-5p/TFF1 轴调控高糖诱导的视网膜色素上皮细胞凋亡。

NFE2/miR-423-5p/TFF1 axis regulates high glucose-induced apoptosis in retinal pigment epithelial cells.

机构信息

Department of Ophthalmology, Second Affiliated Hospital, Zhejiang University School of Medicine, No.88, Jiefang Road, Shangcheng District, Hangzhou, 310003, Zhejiang Province, People's Republic of China.

Department of Ophthalmology, The Third Xiangya Hospital of Central South University, Changsha, 410013, People's Republic of China.

出版信息

BMC Mol Cell Biol. 2019 Aug 27;20(1):39. doi: 10.1186/s12860-019-0223-2.

BACKGROUND

A study has shown that miR-423-5p is highly expressed in proliferative diabetic retinopathy. However, the exact biological functions and mechanisms of miR-423-5p in diabetic retinopathy (DR) progression are currently unclear. This study aimed to investigate the role of miR-423-5p in DR and the underlying mechanism.

RESULTS

Our data demonstrate that the expression of miR-423-5p is significantly increased in HG-induced RPE cells and DR patient plasma. Moreover, the overexpression of miR-423-5p exacerbates HG-induced apoptosis. Mechanistically, our results provide evidence that miR-423-5p directly targets TFF1. MiR-423-5p exerts its effect on HG-induced apoptosis in RPE cells through TFF1, and the NF-κB pathway is involved in the regulatory mechanism. Further analysis revealed that the transcription factor NFE2 regulates miR-423-5p promoter activity. In addition, NFE2 regulates the levels of TFF1 and NF-κB pathway-associated proteins by regulating the expression of miR-423-5p.

CONCLUSION

The NFE2-miR-423-5p-TFF1 axis is a novel molecular mechanism and provides a new direction for the study and treatment of DR.

背景

有研究表明，miR-423-5p 在增殖性糖尿病视网膜病变中高表达。然而，miR-423-5p 在糖尿病视网膜病变（DR）进展中的确切生物学功能和机制目前尚不清楚。本研究旨在探讨 miR-423-5p 在 DR 中的作用及其潜在机制。

结果

我们的数据表明，miR-423-5p 在高糖诱导的 RPE 细胞和 DR 患者血浆中的表达显著增加。此外，miR-423-5p 的过表达加剧了高糖诱导的细胞凋亡。在机制上，我们的结果提供了证据表明，miR-423-5p 可以直接靶向 TFF1。miR-423-5p 通过 TFF1 对 RPE 细胞中高糖诱导的细胞凋亡发挥作用，NF-κB 通路参与了调节机制。进一步分析表明，转录因子 NFE2 调节 miR-423-5p 启动子活性。此外，NFE2 通过调节 miR-423-5p 的表达来调节 TFF1 和 NF-κB 通路相关蛋白的水平。