Analysis of fibulin-3 after exposure to asbestos-like fibers

Our plain-English summary of Analysis of fibulin-3 after exposure to asbestos-like fibers, by V. Rapisarda, R. Caltabiano, G. Musumeci, et al (Environmental Research, 2017).

The study

• Authors: V. Rapisarda, R. Caltabiano, G. Musumeci, P. Castrogiovanni, M. Ferrante, C. Ledda, C. Lombardo, A.C.E. Graziano, V. Cardile, C. Loreto
• Journal: Environmental Research
• Published: 2017;156:381-387
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla. Furthermore, an in vitro model of exposed fluoro-edenite fibroblasts was used to perform functional experiments to better understand the modulation of Fibulin-3 expression. The percentage of immunostained area by Fibulin-3 was very much higher in exposed lungs compared with non-exposed ones. The Fibulin-3 protein level was significantly expressed in primary human lung fibroblasts exposed to 50 and 100µg/ml of fluoro-edenite fibers for 72h, compared to the unexposed controls. The results from the present study further demonstrate the implication of Fibulin-3 during fluoro-edenite exposure. This would endorse our previous results regarding the use of Fibulin-3 as a possible screening biomarker for fluoro-edenite exposed individuals, thereby contributing to the monitoring of the population at risk. The present study also suggested that the Fibulin-3 overexpression may reflect a defensive response of the tissues after exogenous stimuli and may be implicated in cancer development, especially in the context of fluoro-edenite contamination. However, further studies are necessary in order to make Fibulin-3 a customized screening tool.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This laboratory study examined fibulin-3, a protein proposed as a marker for malignant mesothelioma, after exposure to fluoro-edenite. The article describes fluoro-edenite as a natural asbestiform fiber, a fibrous amphibole, from Biancavilla, Sicily. The authors studied lung tissue from 60 sheep that grazed 3 km from Biancavilla and from 10 control sheep that grazed about 50 km from the local stone quarry. Fluoro-edenite fibers were seen in the lungs of the exposed sheep, along with fibrotic lung tissue and a thickened lining of the small airways. In the non-exposed lungs, only traces of fibulin-3 staining were found. In the exposed lungs, both the stained area and the staining intensity were much greater (p less than 0.01). The authors also exposed human lung fibroblasts (connective-tissue cells) grown in the laboratory to fluoro-edenite for 72 hours. At 10 µg/ml, fibulin-3 did not change significantly. At 50 and 100 µg/ml, fibulin-3 levels were significantly higher (p less than 0.05). The authors concluded that this increase may reflect a defensive response of the tissues. They speculated that fibulin-3 may be involved in cancer development, and said further studies are needed before it could become a screening tool.

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: Laboratory study with two parts: staining (immunohistochemistry) of lung tissue from exposed and control sheep, and an experiment on human lung fibroblasts grown in the laboratory (in vitro)
• Who was studied: Sixty sheep of both sexes, randomly selected from six exposed flocks (360 animals) that habitually grazed 3 km from Biancavilla, Sicily, Italy, and ten control sheep from a flock (60 animals) that grazed about 50 km from the Biancavilla stone quarry. All were aged 4.0 to 6.5 years. The study also used primary lines of normal human adult lung fibroblasts. No study dates are given.
• Exposure: Fluoro-edenite (FE), a natural asbestiform fibrous amphibole. The sheep were exposed environmentally by grazing in the Biancavilla area. The human lung fibroblasts were exposed to 10, 50 and 100 µg/ml of fluoro-edenite fibers for 72 hours.
• Main results:
  • In exposed sheep lungs, fluoro-edenite fibers were found in the lung tissue. The interstitium (tissue between the air sacs) appeared fibrotic, and the bronchiolar lining (small airways) was thickened. These changes were more evident where the fibers were deposited.
  • In the lungs of the 10 non-exposed sheep, only traces of fibulin-3 staining were found, too faint for the investigator to see under the microscope.
  • Both high-intensity and low-intensity fibulin-3 staining were much greater in the lungs of exposed sheep than in non-exposed lungs (p less than 0.01). The text does not print the numerical values; they appear only in a graph.
  • The percentage of lung tissue area stained for fibulin-3 was much higher in exposed sheep lungs than in non-exposed ones (p less than 0.01).
  • In human lung fibroblasts, 10 µg/ml of fluoro-edenite caused no significant change in fibulin-3 protein compared with untreated cells.
  • In human lung fibroblasts, 50 and 100 µg/ml of fluoro-edenite produced significantly higher fibulin-3 protein levels than in unexposed cells (p less than 0.05, based on three independent immunoblots).
• The authors' conclusion: The authors concluded that the increase in fibulin-3 seen in the sheep lungs and in human fibroblasts after fluoro-edenite exposure may reflect a defensive response of the tissues to outside stimuli. They speculated that fibulin-3 may be involved in cancer development, especially where fluoro-edenite contamination is present. They said the findings would support their earlier results on fibulin-3 as a possible screening biomarker for people exposed to fluoro-edenite.
• Limitations the authors state:
  • The authors stated that further studies are needed to understand the molecular mechanism involving fibulin-3 and to make it a customized screening tool.

Topics

Medical terms in this study, explained in our Lexicon: Fibulin-3, Mesothelioma, Biancavilla, fluoro-edenite, Amphibole Group, Glycoprotein, Biomarker, Pleural Plaques.

Related studies

• Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1 — C. Loreto, R. Caltabiano, et al. (2020)
• Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2016)
• Prevalence of anti-nuclear autoantibodies in subjects exposed to natural asbestiform fibers: a cross-sectional study — C. Ledda, R. Caltabiano, et al. (2018)
• Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report — R. Caltabiano, C. Loreto, et al. (2018)
• FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study — V. Rapisarda, C. Ledda, et al. (2015)
• Immunohistochemical expression of retinoblastoma and phospho-retinoblastoma protein in sheep lung exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2010)

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