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

Details

• Personal Author:
  Castranova, Vincent ; Dymacek J ; Guo NL ; Mercer RR ; Porter DW ; Qian Y ; Snyder-Talkington BN ; Wolfarth MG
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Genetics Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Pathology Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Author Keywords: Multi Walled Carbon Nanotubes Diseases Etiology Fibrous-bodies Genes Laboratory-animals Lung-disease Lung-fibrosis Lung-irritants MicroRNA Molecular-biology Molecular-structure MRNA Nanotechnology Pathogenesis Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-irritants Respiratory-system-disorders

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  51-64
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045561
• Citation:
  Toxicol Sci 2015 Apr; 144(1):51-64
• Contact Point Address:
  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
• Email:
  yaq2@cdc.gov
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c15c595a64de2bff9579e1c6ddc4ad07cee4427436a6c2f902d77c9d8021c813337fbc9e7568be30518ea200d83eae5cdb51d6ad93d8a6f403fa707f94ff55ad
• Download URL:
  https://stacks.cdc.gov/view/cdc/200935/cdc_200935_DS1.pdf
• File Type:
  [PDF - 515.21 KB ]