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.

The Role of MicroRNAs in Environmental Risk Factors, Noise-Induced Hearing Loss, and Mental Stress

“…In hippocampal HT-22 cells subjected to a cycle of hypoxia/reoxygenation, an increase in ROS production occurs that could be mediated by an increase in miR-200a-3p and miR-200b-3p expression, although the mechanism by which miR-200 miRNAs affect ROS production in neuronal cells is still unclear (205). In B2B human bronchial epithelial cells, it has been shown that members of the let-7 family are downregulated by oxidative stress and, in turn, let-7a overexpression protects cells from the oxidative damage-mediated death by reducing oxidative stress through the direct inhibition of arginase 2 (177). In human Huh-7 hepatocytes, let-7 miRNAs also protect cells from oxidative injury through the direct inhibition of BACH1, a key repressor of the cytoprotective enzyme heme oxygenase 1 (74).…”

Ophiopogonin D attenuates PM2.5‑induced inflammation via suppressing the AMPK/NF‑κB pathway in mouse pulmonary epithelial cells

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