title: Let-7a modulates particulate matter (≤ 2.5 μm)-induced oxidative stress and injury in human airway epithelial cells by targeting arginase 2.
abstract: Epidemiological studies show that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5-mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let-7 family might play a role in PM-mediated pathological processes. In this study, we investigated the role of let-7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let-7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let-7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let-7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3'-untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let-7a against PM2.5-induced injury. In conclusion, let-7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let-7a/ARG2 axis is a likely therapeutic target for PM2.5-induced airway epithelial injury. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin Universtity, 71 the Xinmin Street, Changchun, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin Universtity, 71 the Xinmin Street, Changchun, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin Universtity, 71 the Xinmin Street, Changchun, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pediatrics, The First Hospital of Jilin University, 71 the Xinmin Street, Changchun, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin Universtity, 71 the Xinmin Street, Changchun, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Peng
mesh_terms: D001119:Arginase / Q000037:antagonists & inhibitors* / Q000235:genetics; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D052638:Particulate Matter; D017382:Reactive Oxygen Species; C487931:mirnlet7 microRNA, human; C477631:ARG2 protein, human; D001119:Arginase
keywords: ARG2; PM2.5; airway epithelial cell; let-7a; microRNA; oxidative stress