Mouse serum exosomal proteomic signature in response to asbestos exposure

Our plain-English summary of Mouse serum exosomal proteomic signature in response to asbestos exposure, by P. Munson, Y.W. Lam, M. MacPherson, et al (Journal of Cellular Biochemistry, 2018).

The study

• Authors: P. Munson, Y.W. Lam, M. MacPherson, S. Beuschel, A. Shukla
• Journal: Journal of Cellular Biochemistry
• Published: 2018;119(7):6266-6273
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos-induced diseases like fibrosis and mesothelioma are very aggressive, without any treatment options. These diseases are diagnosed only at the terminal stages due to lack of early stage biomarkers. The recent discovery of exosomes as circulating biomarkers led us to look for exosomal biomarkers of asbestos exposure in mouse blood. In our model, mice were exposed to asbestos as a single bolus dose by oropharyngeal aspiration. Fifty-six days later blood was collected, exosomes were isolated from plasma and characterized and subjected to proteomic analysis using Tandem Mass Tag labeling. We identified many proteins, some of which were more abundant in asbestos exposed mouse serum exosomes, and three selected proteins were validated by immunoblotting. Our study is the first to show that serum exosomal proteomic signatures can reveal some important proteins relevant to asbestos exposure that have the potential to be validated as candidate biomarkers. We hope to extrapolate the positive findings of this study to humans in future studies.

© 2018 Wiley Periodicals, Inc.

In plain English

This was an experiment in mice, not people. The authors gave C57/Bl6 mice a single dose of crocidolite asbestos, or saline, into the airway by oropharyngeal aspiration. After 56 days they collected blood serum, isolated exosomes (tiny membrane-bound particles released by cells), and measured the proteins in these exosome preparations. They quantified 376 proteins, comparing 4 saline-treated mice with 5 asbestos-exposed mice. Only a few proteins differed between the groups with statistical significance (p less than 0.05), which the authors attributed to variation among individual animals. Among the 15 proteins they listed, haptoglobin had the largest fold change (3.559 times higher in the asbestos group), but this was not statistically significant (p = 0.232). On immunoblot checks in the same mice, fibulin-1 was increased in 4 of 5 asbestos-exposed mice, ceruloplasmin in all 5, and haptoglobin in 3 of 5. The authors concluded that serum exosome protein profiles can reveal proteins related to asbestos exposure that could be tested as candidate biomarkers. They hope to extend the work to humans. They described the possible roles of these proteins as speculative.

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 (mouse exposure study with proteomic analysis of blood serum exosomes)
• Who was studied: C57/Bl6 mice, 5 per group, at the University of Vermont. The proteomic comparison used 4 saline-exposed control mice and 5 asbestos-exposed mice. Study dates are not given.
• Exposure: Crocidolite asbestos (NIEHS reference sample), or saline for controls (50 µL), given as a single bolus dose by oropharyngeal aspiration. Blood was collected 56 days later. The mass dose of asbestos is not stated in the text.
• Main results:
  • 376 proteins were quantified in the serum exosome preparations.
  • Only a few proteins differed in abundance in the asbestos group with statistical significance (p less than 0.05). The authors attributed this to biological variation among individual animals.
  • Among the top 15 proteins listed, haptoglobin had the largest fold change in the asbestos group compared with controls (3.559), with a p-value of 0.232 (not statistically significant).
  • On immunoblot of the same mice, increased exosomal fibulin-1 was seen in 4 of 5 asbestos-exposed mice, ceruloplasmin in all 5, and haptoglobin in 3 of 5.
  • The isolated particles had a median size of 68.1 nm and carried the exosome markers CD9 and CD81.
• The authors' conclusion: The authors concluded that serum exosomal protein signatures can reveal proteins relevant to asbestos exposure that could be validated as candidate biomarkers. They hope to extend the findings to humans in future studies.
• Limitations the authors state:
  • The authors noted heterogeneous effects among the asbestos-exposed animals.
  • The authors stated that the possible consequences of the exosomal proteins they discussed are speculative and need further study.
  • No loading controls were available for the immunoblots because the proteins are secreted. Equal loading was assessed by Ponceau staining instead.

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Fibrosis, Mesothelioma, Biomarker, Discovery.

Related studies

• Silica binds serum proteins resulting in a shift of the dose-response for silica-induced chemokine expression in an alveolar type II cell line — E.G. Barrett, C. Johnston, et al. (1999)
• Exosomal miR-16-5p as a target for malignant mesothelioma — P.B. Munson, E.M. Hall, et al. (2019)
• Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo — D.W. Greening, H. Ji, et al. (2016)
• Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells — P. Munson, Y.W. Lam, et al. (2018)
• Selective adsorption of serum proteins by chrysotile and crocidolite — F. Valerio, D. Balducci, et al. (1986)
• Serum protein concentrations and respiratory tract abnormalities following short-term exposure to amosite: a comparison between former asbestos workers and unexposed controls — D.R. Nash, N.G. Fortson, et al. (1981)

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