Jin Li1,2, Qiulian Zhou1,2, Yajun Liang2, Wen Pan2, Yihua Bei2, Yuhui Zhang3, Jinhua Wang1, Zheng Jiao1. 1. Shanghai Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China. 2. Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China. 3. State Key Laboratory of Cardiovascular Disease, Heart Failure Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Abstract
BACKGROUND: Environmental exposure to particulate matter 2.5 (PM2.5) threatens public health, which has caused worldwide concerns. MicroRNAs (miRNAs, miRs) participate in multiple biological regulation. Among them, miR-486 has been reported to be a beneficial molecule for cell survival in various cell types. However, the potential function of miR-486 in PM2.5-induced cytotoxic is still uncertain. METHODS: The expression of miR-486 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) after A549 cells incubated with PM2.5. Then TUNEL staining and DCFH-DA fluorescence were used to test the apoptosis and ROS generation of A549 cells after exposed to PM2.5 with miR-486 mimic. Western blot was performed to determine the expression of Bax/Bcl2 ratio. In addition, western blot and rescue experiments were conducted to determine the target gene of miR-486. RESULTS: After treated with PM2.5, the expression of miR-486 was decreased. And miR-486 mimic treatment reduced cell apoptosis and reactive oxygen species (ROS) generation induced by PM2.5 exposure. Further studies showed that miR-486 negatively regulated the protein levels of PTEN and FOXO1. Rescue experiments demonstrated that PTEN and FOXO1 mediated the protective effects of miR-486 in PM2.5-treated human lung alveolar epithelial A549 cells. CONCLUSIONS: Collectively, our findings identify that miR-486 relieves PM2.5-induced cell injury by targeting PTEN and FOXO1 in human lung alveolar epithelial A549 cells.
BACKGROUND: Environmental exposure to particulate matter 2.5 (PM2.5) threatens public health, which has caused worldwide concerns. MicroRNAs (miRNAs, miRs) participate in multiple biological regulation. Among them, miR-486 has been reported to be a beneficial molecule for cell survival in various cell types. However, the potential function of miR-486 in PM2.5-induced cytotoxic is still uncertain. METHODS: The expression of miR-486 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) after A549 cells incubated with PM2.5. Then TUNEL staining and DCFH-DA fluorescence were used to test the apoptosis and ROS generation of A549 cells after exposed to PM2.5 with miR-486 mimic. Western blot was performed to determine the expression of Bax/Bcl2 ratio. In addition, western blot and rescue experiments were conducted to determine the target gene of miR-486. RESULTS: After treated with PM2.5, the expression of miR-486 was decreased. And miR-486 mimic treatment reduced cell apoptosis and reactive oxygen species (ROS) generation induced by PM2.5 exposure. Further studies showed that miR-486 negatively regulated the protein levels of PTEN and FOXO1. Rescue experiments demonstrated that PTEN and FOXO1 mediated the protective effects of miR-486 in PM2.5-treated human lung alveolar epithelial A549 cells. CONCLUSIONS: Collectively, our findings identify that miR-486 relieves PM2.5-induced cell injury by targeting PTEN and FOXO1 in human lung alveolar epithelial A549 cells.
Authors: Serena Fossati; Andrea Baccarelli; Antonella Zanobetti; Mirjam Hoxha; Pantel S Vokonas; Robert O Wright; Joel Schwartz Journal: Epidemiology Date: 2014-01 Impact factor: 4.822