Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells.
Bottom Line: We measured the expression of 88 MV-associated miRNAs by real-time polymerase chain reaction.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.
Affiliation: Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy.Show MeSH
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Mentions: In this study, we evaluated the expression of 88 MV-associated microRNAs, isolated from the plasma of healthy, electric steel plant facility workers, in response to PM exposure. We identified two miRNAs, miR-128 and miR-302c, that may be involved in the molecular response to air pollution. To provide information about the potential tissue of origin of the miRNAs found in plasma MVs, we evaluated expression of these two miRNAs in vitro in MVs released from A549 pulmonary cells treated with PM. The in vitro experiment showed that PM induced the expression of miR-128 in A549, but not of miR-302c, which was not expressed in MVs from A549 cells, in RNA extracted from A549 cells, or in reference RNA from lung tissue. Taken together, these results are consistent with the hypothesis, summarized in Fig.4, that PM exposure induces the release of specific miRNAs (e.g., miR-128) in MVs generated from alveolar or other lung cells and that such MV-contained miRNAs can be detected in plasma. In turn, MV-contained miRNAs could travel to tissues critical to the PM cardiovascular events, such as blood and tissue leukocytes, endothelial cells and other cardiovascular tissues to reprogram their gene expression and contribute to determine PM-induced outcomes, such as inflammation, blood clotting or atherosclerosis. While our results indicate that PM induces release in plasma of miRNAs originating from lung tissues, further research is needed to determine whether they participate in the pathways leading to adverse health effects.
Affiliation: Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Epidemiology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy.