title: mRNA and miRNA regulatory networks reflective of multi-walled carbon nanotube-induced lung inflammatory and fibrotic pathologies in mice.
abstract: Multi-walled carbon nanotubes (MWCNTs) are known for their transient inflammatory and progressive fibrotic pulmonary effects; however, the mechanisms underlying these pathologies are unknown. In this study, we used time-series microarray data of global lung mRNA and miRNA expression isolated from C57BL/6J mice exposed by pharyngeal aspiration to vehicle or 10, 20, 40, or 80 µg MWCNT at 1, 7, 28, or 56 days post-exposure to determine miRNA and mRNA regulatory networks that are potentially involved in MWCNT-induced inflammatory and fibrotic lung etiology. Using a non-negative matrix factorization method, we determined mRNAs and miRNAs with expression profiles associated with pathology patterns of MWCNT-induced inflammation (based on bronchoalveolar lavage score) and fibrosis (based on Sirius Red staining measured with quantitative morphometric analysis). Potential binding targets between pathology-related mRNAs and miRNAs were identified using Ingenuity Pathway Analysis and the miRTarBase, miRecords, and TargetScan databases. Using these experimentally validated and predicted binding targets, we were able to build molecular signaling networks that are potentially reflective of and play a role in MWCNT-induced lung inflammatory and fibrotic pathology. As understanding the regulatory networks between mRNAs and miRNAs in different disease states would be beneficial for understanding the complex mechanisms of pathogenesis, these identified genes and pathways may be useful for determining biomarkers of MWCNT-induced lung inflammation and fibrosis for early detection of disease.
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300.
authors.forename: Julian
authors.initials: J
authors.lastname: Dymacek
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300.
authors.forename: Brandi N
authors.initials: BN
authors.lastname: Snyder-Talkington
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wolfarth
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300 lguo@hsc.wvu.edu.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.affiliation: *Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia 26506-6070, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506 and Department of Occupational and Environmental Health Science, School of Public Health, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9300 lguo@hsc.wvu.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Guo
mesh_terms: D000818:Animals; D019295:Computational Biology; D030541:Databases, Genetic; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D037742:Nanotubes, Carbon; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D005819:Genetic Markers; D018836:Inflammation Mediators; D035683:MicroRNAs; D037742:Nanotubes, Carbon; D012333:RNA, Messenger
keywords: mRNA; microRNA; multi-walled carbon nanotubes