miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells
机构：[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
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.
基金：
This work was generously supported by grants from the National Natural Science Foundation of China (Nos. 81371055 and 81570859 to Q.J.); Grants from the Science and Technology Development Project Fund of Nanjing (Grant No. 201402051 to Q.J.); Grants from the Six Talent Peaks Project Fund of Jiangsu province (Grant No. WS- 073 to Q.J.).
第一作者机构：[1]Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu’xi, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu’xi, China[2]The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China
推荐引用方式(GB/T 7714)：
Li-Bo Cheng,Ke-ran Li,Nan Yi,et al.miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells[J].ONCOTARGET.2017,8(8):13186-13194.doi:10.18632/oncotarget.14489.
APA：
Li-Bo Cheng,Ke-ran Li,Nan Yi,Xiu-miao Li,Feng Wang...&Zhi-feng Wu.(2017).miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells.ONCOTARGET,8,(8)
MLA：
Li-Bo Cheng,et al."miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells".ONCOTARGET 8..8(2017):13186-13194
医学