Release of MicroRNAs into body fluids from ten organs of mice exposed to cigarette smoke

Alberto Izzotti, Mariagrazia Longobardi, Sebastiano La Maestra, Rosanna T. Micale, Alessandra Pulliero, Anna Camoirano, Marta Geretto, Francesco D'Agostini, Roumen Balansky, Mark Steven Miller, Vernon E. Steele, Silvio de Flora

Research output: Contribution to journalArticle

Abstract

Purpose: MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures. Experimental design: Using microarray analyses, we measured 1135 microRNAs in 10 organs and 3 body fluids of mice that were either unexposed or exposed to mainstream cigarette smoke for up to 8 weeks. The results obtained with selected miRNAs were validated by qPCR. Results: The lung was the main target affected by smoke (190 dysregulated miRNAs), followed by skeletal muscle (180), liver (138), blood serum (109), kidney (96), spleen (89), stomach (36), heart (33), bronchoalveolar lavage fluid (32), urine (27), urinary bladder (12), colon (5), and brain (0). Skeletal muscle, kidney, and lung were the most important sources of smoke-altered microRNAs in blood serum, urine, and bronchoalveolar lavage fluid, respectively. Conclusions: microRNA expression analysis was able to identify target organs after just 8 weeks of exposure to smoke, well before the occurrence of any detectable histopathological alteration. The present translational study validates the use of body fluid microRNAs as biomarkers applicable to human biomonitoring for mechanistic studies, diagnostic purposes, preventive medicine, and therapeutic strategies.

Original languageEnglish
Pages (from-to)2147-2160
Number of pages14
JournalTheranostics
Volume8
Issue number8
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Body fluids
  • Cigarette smoke
  • Interorgan distribution
  • MicroRNAs

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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  • Cite this

    Izzotti, A., Longobardi, M., La Maestra, S., Micale, R. T., Pulliero, A., Camoirano, A., Geretto, M., D'Agostini, F., Balansky, R., Miller, M. S., Steele, V. E., & de Flora, S. (2018). Release of MicroRNAs into body fluids from ten organs of mice exposed to cigarette smoke. Theranostics, 8(8), 2147-2160. https://doi.org/10.7150/thno.22726