miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells
| Autor: | Ying-shun Pan, Qin Jiang, Xiu-Miao Li, Bo Xue, Feng Wang, Ke-ran Li, Jin Yao, Li-bo Cheng, Zhi-feng Wu, Nan Yi |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Retinal Ganglion Cells
0301 basic medicine Keap1 Programmed cell death Cell Survival NF-E2-Related Factor 2 Ultraviolet Rays Blotting Western Apoptosis Nrf2 signaling Retinal Pigment Epithelium medicine.disease_cause Retinal ganglion Cell Line 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation miRNA-141 retinal pigment epithelium cells medicine oxidative stress Humans Cells Cultured chemistry.chemical_classification Reactive oxygen species Kelch-Like ECH-Associated Protein 1 Retinal pigment epithelium Reverse Transcriptase Polymerase Chain Reaction business.industry Anatomy respiratory system Cytoprotection Molecular biology UV MicroRNAs 030104 developmental biology GCLC medicine.anatomical_structure Gene Expression Regulation Oncology chemistry 030220 oncology & carcinogenesis RNA Interference Reactive Oxygen Species business Oxidative stress Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.14489 |
| Popis: | // Li-Bo Cheng 1, * , Ke-ran Li 2, * , Nan Yi 3, * , Xiu-miao Li 2,* , Feng Wang 1 , Bo Xue 1 , Ying-shun Pan 1 , Jin Yao 2 , Qin Jiang 2 , Zhi-feng Wu 1 1 Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu’xi, China 2 The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China 3 Department of Hand and Foot Surgery, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China * Co-first authors Correspondence to: Qin Jiang, email: Jqin710@vip.sina.com Jin Yao, email: dryaojin@yahoo.com Zhi-feng Wu, email: wuzfwuxieye@163.com Keywords: miRNA-141, UV, oxidative stress, Keap1, Nrf2 signaling, retinal pigment epithelium cells, retinal ganglion cells Received: October 24, 2016 Accepted: December 07, 2016 Published: January 04, 2017 ABSTRACT Activation of NF-E2-related factor 2 (Nrf2) signaling could protect cells from ultra violet (UV) radiation. We aim to provoke Nrf2 activation via downregulating its inhibitor Keap1 by microRNA-141 (“miR-141”). In both human retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs), forced-expression of miR-141 downregulated Keap1, causing Nrf2 stabilization, accumulation and nuclear translocation, which led to transcription of multiple antioxidant-responsive element (ARE) genes (HO1, NOQ1 and GCLC). Further, UV-induced reactive oxygen species (ROS) production and cell death were significantly attenuated in miR-141-expressing RPEs and RGCs. On the other hand, depletion of miR-141 via expressing its inhibitor antagomiR-141 led to Keap1 upregulation and Nrf2 degradation, which aggravated UV-induced death of RPEs and RGCs. Significantly, Nrf2 shRNA knockdown almost abolished miR-141-mediated cytoprotection against UV in RPEs. These results demonstrate that miR-141 targets Keap1 to activate Nrf2 signaling, which protects RPEs and RGCs from UV radiation. |
| Databáze: | OpenAIRE |
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