miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells.
miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells.
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DOI：
10.18632/oncotarget.14489
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发表时间：
2017-02-21
期刊：
影响因子：
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通讯作者：
Wu ZF
中科院分区：
文献类型：
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作者：
Cheng LB;Li KR;Yi N;Li XM;Wang F;Xue B;Pan YS;Yao J;Jiang Q;Wu ZF
NF-E2相关因子2（Nrf 2）信号的激活可以保护细胞免受紫外线（UV）辐射。我们的目标是通过microRNA-141（“miR-141”）下调其抑制剂Keap 1来激发Nrf 2激活。在人视网膜色素上皮细胞（RPE）和视网膜神经节细胞（RGC）中，miR-141的强制表达下调Keap 1，引起Nrf 2稳定、积累和核转位，从而导致多个抗氧化剂反应元件（ARE）基因（HO 1、NOQ 1和GCLC）的转录。此外，在表达miR-141的RPE和RGC中，UV诱导的活性氧（ROS）产生和细胞死亡显著减弱。另一方面，通过表达miR-141的抑制剂miR-141来消耗miR-141导致Keap 1上调和Nrf 2降解，这加重了UV诱导的RPE和RGC死亡。值得注意的是，Nrf 2 shRNA敲低几乎消除了RPE中miR-141介导的抗UV细胞保护作用。这些结果表明，miR-141靶向Keap 1以激活Nrf 2信号传导，从而保护RPE和RGCs免受UV辐射。
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.