Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study

Our plain-English summary of Similar and Differential Canonical Pathways and Biological Processes Associated With Multiwalled Carbon Nanotube and Asbestos-Induced Pulmonary Fibrosis: A 1-Year Postexposure Study, by J.M. Dymacek, B.N. Snyder-Talkington, R. Raese, et al (International Journal of Toxicology, 2018).

The study

• Authors: J.M. Dymacek, B.N. Snyder-Talkington, R. Raese, C. Dong, S. Singh, D.W. Porter, B. Ducatman, M.G. Wolfarth, M.E. Andrew, L. Battelli, V. Castranova, Y. Qian, N.L. Guo
• Journal: International Journal of Toxicology
• Published: 2018;37(4):276-284
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Respiratory exposure to multiwalled carbon nanotubes (MWCNT) or asbestos results in fibrosis; however, the mechanisms to reach this end point may be different. A previous study by our group identified pulmonary effects and significantly altered messenger RNA (mRNA) signaling pathways following exposure to 1, 10, 40, and 80 µg MWCNT and 120 µg crocidolite asbestos on mouse lungs over time at 1-month, 6-month, and 1-year postexposure following pulmonary aspiration. As a continuation to the above study, this current study took an in-depth look at the signaling pathways involved in fibrosis development at a single time point, 1 year, and exposure, 40 µg MWCNT, the lowest exposure at which fibrosis was pathologically evident. The 120 µg asbestos exposure was included to compare MWCNT-induced fibrosis with asbestos-induced fibrosis. A previously validated computational model was used to identify mRNAs with expression profiles matching the fibrosis pathology patterns from exposed mouse lungs. mRNAs that matched the pathology patterns were then input into ingenuity pathway analysis to determine potential signaling pathways and physiological disease functions inherent to MWCNT and asbestos exposure. Both MWCNT and asbestos exposure induced changes in mouse lungs regarding gene expression, cell proliferation, and survival, while MWCNT uniquely induced alterations in pathways involved in oxidative phosphorylation, mitochondrial dysfunction, and transcription. Asbestos exposure produced unique alterations in pathways involved in sustained inflammation. Although typically considered similar due to scale and fiber-like appearance, the different compositional properties inherent to either MWCNT or asbestos may play a role in their ability to induce fibrosis after pulmonary exposure.

In plain English

This laboratory study in mice reanalyzed gene-activity data from the authors' group's earlier study. In that study, mice were given multiwalled carbon nanotubes (MWCNT) or crocidolite asbestos into the lungs by aspiration and examined at 1 month, 6 months and 1 year. This analysis used 40 micrograms of MWCNT, the lowest exposure at which fibrosis was significantly evident on pathology at 1 year, and compared it with 120 micrograms of crocidolite asbestos. A computer model picked out genes whose activity matched the lung fibrosis: 2,462 for MWCNT, 3,669 for asbestos and 3,551 for both. Asbestos genes clustered in pathways such as nitric oxide and reactive oxygen species production in macrophages, and inflammation genes were significantly changed. MWCNT uniquely altered pathways involving oxidative phosphorylation, mitochondrial dysfunction and transcription, plus ribosomal proteins. The authors concluded that asbestos may lead to fibrosis through a continuous inflammatory process. They noted that whole lungs were analyzed rather than specific cell types, and that validation of the findings is ongoing.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: a computational reanalysis of gene-expression (mRNA microarray) data from the same research group's earlier mouse study, matching gene activity over time to fibrosis seen in lung tissue
• Who was studied: Mice exposed by pulmonary aspiration and examined at 1 month, 6 months and 1 year after exposure. The number and strain of mice are not given in this article (methods are referred to the earlier study).
• Exposure: Multiwalled carbon nanotubes at 40 micrograms, the lowest exposure at which fibrosis was significantly evident on pathology at 1 year after exposure, compared with 120 micrograms of crocidolite asbestos. The article text prints these doses as 'mg'; see text_problems.
• Main results:
  • 2,462 genes matched the MWCNT 40 microgram fibrosis pattern and 3,669 genes matched the asbestos fibrosis pattern.
  • 3,551 genes matched both the MWCNT 40 microgram and the asbestos fibrosis patterns.
  • Pathways more associated with the asbestos pattern than the MWCNT pattern included production of nitric oxide and reactive oxygen species in macrophages, and B-cell receptor signaling.
  • Pathways more associated with the MWCNT 40 microgram pattern than the asbestos pattern included EIF2 signaling, regulation of eIF4 and p70S6K signaling, and hereditary breast cancer signaling.
  • MWCNT uniquely altered pathways involved in oxidative phosphorylation, mitochondrial dysfunction and transcription.
  • Asbestos exposure uniquely altered pathways involved in sustained inflammation.
  • Pathways linked to both the MWCNT and asbestos patterns included NF-kappa-B signaling, G-protein-coupled receptor signaling, and the role of NFAT in cardiac hypertrophy.
  • Changes in ribosomal protein genes were found after MWCNT exposure but not after asbestos exposure.
  • In the asbestos-associated analysis, genes involved in inflammation (CCL3, CCL5, NFKBIA, IL1B) and in apoptosis (APAF1, LRP1) were significantly upregulated or downregulated.
  • No specific fibrosis-related genes were significantly changed in the top pathways linked only to MWCNT.
• The authors' conclusion: The authors concluded that asbestos exposure may lead to fibrosis through a continuous inflammatory process, while MWCNT lead to fibrosis through different means.
• Limitations the authors state:
  • Whole lungs were used for the gene analysis instead of specific cell types.
  • The identified pathways and cellular changes have not yet been validated; the authors say validation is ongoing.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, Fibrosis, Crocidolite, Asbestos Exposure, Pathology, Inflammation.

Related studies

• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway — T. Chen, H. Nie, et al. (2014)
• Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons — A.A. Shvedova, N. Yanamala, et al. (2014)
• Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs — P. Kinaret, M. Ilves, et al. (2017)
• A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice — E.J. Park, J. Roh, et al. (2011)
• Integration of inflammation, fibrosis, and cancer induced by carbon nanotubes — J. Dong, Q. Ma (2019)

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