title: miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells.
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.
authors.affiliation: Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu'xi, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Cheng
authors.affiliation: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Ke-Ran
authors.initials: KR
authors.lastname: Li
authors.affiliation: Department of Hand and Foot Surgery, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yi
authors.affiliation: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xiu-Miao
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu'xi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu'xi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu'xi, China.
authors.forename: Ying-Shun
authors.initials: YS
authors.lastname: Pan
authors.affiliation: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.affiliation: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Wuxi Second Hospital, Nanjing Medical University, Wu'xi, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species
keywords: Keap1; Nrf2 signaling; UV; miRNA-141; oxidative stress; retinal ganglion cells; retinal pigment epithelium cells