Carbon black nanoparticle intratracheal installation results in large and sustained changes in the expression of miR-135b in mouse lung

MicroRNAs (miRNA) are important noncoding regulatory molecules that bind target messenger RNA (mRNA), primarily affecting their translation into protein. Because miRNAs can simultaneously target hundreds of mRNAs, subtle changes in their expression can elicit important cellular effects. Little is known about the role of miRNAs in pulmonary responses to inhaled particulate matter. We studied pulmonary global miRNA responses to Printex 90 carbon black nanoparticles in (1) nonpregnant C57BL/6 female mice instilled with vehicle or a single dose of 0.162 mg and euthanized 1, 3, and 28 days post-exposure, and (2) C57BL/6Bom Tac dams instilled with vehicle or a cumulative dose of 0.268 mg (four separate instillations of vehicle or 0.067 mg Printex 90 during pregnancy) and euthanized at weaning (2627 days postexposure). We measured similar expression profiles in both exposure scenarios, with marked increases in miR-135b and subtle changes in miR-21 and miR-146b. All three miRNAs were confirmed in nonpregnant females by RT-PCR, whereas only miR-135b was confirmed in the dams. Target analysis revealed no concomitant changes in established and predicted targets of miR-135b, miR-21, or miR-146b. Analysis of potentially perturbed pathways did not reveal changes that would suggest down-stream miRNA effects. The reasons for the lack of association between miRNA and transcript profiles may be related to the complexity of miRNA function and fate, or to the possibility that targets may differ from those already established or predicted in silico. We hypothesize that changes in the expression of these miRNAs may be associated with resolution of pulmonary inflammation, but future work will be necessary to precisely identify specific targets of these miRNAs in lungs. Environ. Mol. Mutagen., 2012. (c) 2012 Wiley Periodicals, Inc.