title: Role of miR-155 in fluorooctane sulfonate-induced oxidative hepatic damage via the Nrf2-dependent pathway.
abstract: Studies demonstrated that perfluorooctane sulfonate (PFOS) tends to accumulate in the liver and is capable to cause hepatomegaly. In the present study, we investigated the roles of miR-155 in PFOS-induced hepatotoxicity in SD rats and HepG2 cells. Male SD rats were orally administrated with PFOS at 1 or 10mg/kg/day for 28 days while HepG2 cells were treated with 0-50 μM of PFOS for 24h or 50 μM of PFOS for 1, 3, 6, 12 or 24h, respectively. We found that PFOS significantly increased the liver weight and serum alanine transaminase (ALT) and aspartate amino transferase (AST) levels in rats. Morphologically, PFOS caused actin filament remodeling and endothelial permeability changes in the liver. Moreover, PFOS triggered reactive oxygen species (ROS) generation and induced apoptosis in both in vivo and in vitro assays. Immunoblotting data showed that NF-E2-related factor-2 (Nrf2) expression and activation and its target genes were all suppressed by PFOS in the liver and HepG2 cells. However, PFOS significantly increased miR-155 expression. Further studies showed that pretreatment of HepG2 cells with catalase significantly decreased miR-155 expression and substantially increased Nrf2 expression and activation, resulting in reduction of PFOS-induced cytotoxicity and oxidative stress. Taken together, these results indicated that miR-155 plays an important role in the PFOS-induced hepatotoxicity by disrupting Nrf2/ARE signaling pathway.
authors: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
authors: Chong
authors: C
authors: Wan
authors: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
authors: Rui
authors: R
authors: Han
authors: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
authors: Limin
authors: L
authors: Liu
authors: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: zhangfang@ucas.ac.cn.
authors: Fang
authors: F
authors: Zhang
authors: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
authors: Fang
authors: F
authors: Li
authors: State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
authors: Mingdeng
authors: M
authors: Xiang
authors: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: dingwj@ucas.ac.cn.
authors: Wenjun
authors: W
authors: Ding
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D017738:Alkanesulfonic Acids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D009929:Organ Size; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; C580597:MIRN155 microRNA, rat; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; C076994:perfluorooctane sulfonic acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Hepatotoxicity; Nrf2; Oxidative stress; PFOS; miR155