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Analysis of fibulin-3 after exposure to asbestos-like fibers
- Rapisarda, Venerando, Caltabiano, Rosario, Musumeci, Giuseppe, Castrogiovanni, Paola, Ferrante, Margherita, Ledda, Caterina, Lombardo, Claudia, Graziano, Adriana Carol Eleonora, Cardile, Venera, Loreto, Carla
- Environmental research 2017 v.156 pp. 381-387
- at-risk population, biomarkers, carcinogenesis, extracellular matrix, fibroblasts, glycoproteins, immunohistochemistry, lungs, mesothelioma, models, monitoring, protein content, quarries, screening, sheep, toxicity, Italy, Sicily
- 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.