Research Papers:
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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Abstract
Li-Bo Cheng1,*, Ke-ran Li2,*, Nan Yi3,*, Xiu-miao Li2,*, Feng Wang1, Bo Xue1, Ying-shun Pan1, Jin Yao2, Qin Jiang2, Zhi-feng Wu1
1Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu’xi, China
2The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China
3Department of Hand and Foot Surgery, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
*Co-first authors
Correspondence to:
Qin Jiang, email: [email protected]
Jin Yao, email: [email protected]
Zhi-feng Wu, email: [email protected]
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.
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PII: 14489