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mRNA and miRNA regulatory networks reflective of multi-walled carbon nanotube-induced lung inflammatory and fibrotic pathologies in mice.

Authors
Dymacek-J; Snyder-Talkington-BN; Porter-DW; Mercer-RR; Wolfarth-MG; Castranova-V; Qian-Y; Guo-NL
Source
Toxicol Sci 2015 Apr; 144(1):51-64
NIOSHTIC No.
20045561
Abstract
Multi-walled carbon nanotubes (MWCNT) 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 ug MWCNT at 1, 7, 28, or 56 days post-exposure to determine miRNA andmRNA 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 upon bronchoalveolar lavage score) and fibrosis (based upon 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.
Keywords
Nanotechnology; Fibrous-bodies; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Respiration; Respiratory-system-disorders; Respiratory-irritants; Pathology; Lung; Lung-disease; Lung-fibrosis; Lung-irritants; Animals; Laboratory-animals; Etiology; Molecular-structure; Molecular-biology; Pathogenesis; Genes; Biomarkers; Diseases; Author Keywords: Multi Walled Carbon Nanotubes; mRNA; microRNA
Contact
Yong Qian, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888
CODEN
TOSCF2
Publication Date
20150401
Document Type
Journal Article
Email Address
yaq2@cdc.gov
Fiscal Year
2015
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicological Sciences
State
WV
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