Superfund Research Program
Toxicological Impact of Mine Tailings Dust on Lung Epithelial Barrier Function
Project Leader: Robert Clark Lantz
Co-Investigators: Scott Boitano, Donna D. Zhang
Grant Number: P42ES004940
Funding Period: 2005-2020
Final Progress Reports
Pregnant females and children may be more susceptible to exposures than adults. The research team has developed cell and animal model systems to determine the effects of early life inhalation exposures to metal containing dusts on adult lung disease. Researchers previously reported that continuous exposures from conception through early postnatal periods led to the greatest changes in lung function (Lantz, 2017). During the past year researchers have shown that a protein that is a master regulator of lung cell phenotypes, transforming growth factor Beta 1 (TGFB1), is greatly up regulated both in the lung and in serum following dust inhalation during development. In addition other proteins that are in pathways regulated by TGFB1 are also altered. These proteins can control production of extracellular matrix, matrix degradation proteases and smooth muscle, alterations that researchers have noted around airways following exposure. Researchers have also tested alterations in protein levels in children exposed to arsenic and have seen alterations of matrix proteins in this human population as well (Smeester 2016). Researchers are testing how the dusts cause these increases. The hypothesis is that arsenic, and potentially other components of the dust, activate production of oxygen radicals through increased expression of an enzyme called NADPH oxidase 4 (NOX4). To date researchers have shown that arsenic increases levels of NOX4 in the airway cells. The next step will be to show that inhibition of the NOX4 expression will reduce expression of TGFB1 and reduce dust exposure induced alterations in pulmonary structure and function.