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. 2015 Jan;35(1):59-67.
doi: 10.1002/jat.2987. Epub 2014 Feb 7.

Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells

Valentina Bollati  1 , Laura Angelici, Giovanna Rizzo, Laura Pergoli, Federica Rota, Mirjam Hoxha, Francesco Nordio, Matteo Bonzini, Letizia Tarantini, Laura Cantone, Angela C Pesatori, Pietro Apostoli, Andrea A Baccarelli, Pier Alberto Bertazzi
Affiliations

Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells

Valentina Bollati et al. J Appl Toxicol. 2015 Jan.

Abstract

Cardiovascular disease risk has been consistently linked with particulate matter (PM) exposure. Cell-derived microvesicles (MVs) are released into plasma and transfer microRNAs (miRNAs) between tissues. MVs can be produced by the respiratory system in response to proinflammatory triggers, enter the circulatory system and remotely modify gene expression in cardiovascular tissues. However, whether PM affects MV signaling has never been investigated. In this study, we evaluated expression of microRNAs contained within plasma MVs upon PM exposure both in vivo and in vitro. In the in vivo study, we isolated plasma MVs from healthy steel plant workers before and after workplace PM exposure. We measured the expression of 88 MV-associated miRNAs by real-time polymerase chain reaction. To assess a possible source of the MV miRNAs identified in vivo, we measured their miRNA expression in PM-treated A549 pulmonary cell lines in vitro. MiRNA profiling of plasma MVs showed 5.62- and 13.95-fold increased expression of miR-128 and miR-302c, respectively, after 3 days of workplace PM exposure (P < 0.001). According to Ingenuity Pathway Analysis, miR-128 is part of coronary artery disease pathways, and miR-302c is part of coronary artery disease, cardiac hypertrophy and heart failure pathways. In vitro experiments confirmed a dose-dependent expression of miR-128 in MVs released from A549 cells after 6 h of PM treatment (P = 0.030). MiR-302c was expressed neither from A549 cells nor in reference lung RNA. These results suggest novel PM-activated molecular mechanisms that may mediate the effects of air pollution and could lead to the identification of new diagnostic and therapeutic interventions.

Keywords: A549 cells; Particulate matter; microRNAs; microvesicles; steel plant workers.

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Figures

Figure 1
Figure 1
Volcano plot representing differential microRNA expression in plasma microvesicles of steel plant workers pre- and postexposure.
Figure 2
Figure 2
Growth profile of A549 cells treated with increasing doses of PM10.
Figure 3
Figure 3
miR-128 expression in microvesicles purified from culture media of A549 cells treated with increasing doses of PM10 at different times.
Figure 4
Figure 4
Possible roles of plasma microvesicle microRNAs in mediating cardiovascular effects of particular matter.
See this image and copyright information in PMC

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