
That cigarette smoke exposure is associated with the development and severity of COPD is nothing new to physicians, but a new study examining the effects of cadmium, a highly toxic metal and pollutant found in cigarettes, could offer direction on potential therapeutic targets to be explored in cadmium exposure and subsequent lung injury.
Researchers at the University of Alabama at Birmingham showed how a low dose of cadmium produces a deleterious stress in lung epithelial cells. The research, published in Scientific Reports and led by Veena Antony, MD, a professor in the UAB Department of Medicine, focuses on microRNA-381 and the expression of a chloride channel gene called AN01 in lung tissue samples and airway epithelial cells.
AN01 helps produce mucus in the airway, but overproduction of mucus in chronic lung disease can lead to airway thickening and mucus blockage, adding to the severity of the disease.
Researchers compared lung tissue samples from nine never smokers, who had zero history of cigarette smoking, and samples from 13 smokers with COPD who had a history of smoking from 15 to 25 years per person. The study found that the smokers had upregulated AN01 expression in airway epithelial cells compared to the never smokers.
In addition, airway epithelial cells in a bronchoalveolar lavage fluid from one non-COPD subject and one smoker with COPD showed greater AN01 expression in the COPD subject cells.
The researchers then tested the direct effect of very low doses of cadmium on normal human airway epithelial cells. Two weeks of exposure to 0.5 or 1.0 micromolar cadmium chloride in the liquid layer increased expression of AN01 by 12 to 14 times.
Researchers used a synthetic inhibitor for microRNA-381 to inhibit the expression of microRNA-381 in primary human airway epithelial cells from subjects with COPD and found that ANO1 expression was upregulated significantly. In contrast, adding a microRNA-381-mimic — a synthetic RNA that acts like microRNA-381 to increase the amount of negative regulation — to those cells decreased ANO1 expression. These results strengthened the premise of the UAB researchers that cadmium negatively regulates microRNA-381 expression to upregulate ANO1 expression in airway epithelial cells.
“The interaction of cadmium, microRNA-281 and AN01 suggests that microRNAs may act as potential therapeutic targets to be explored further in cadmium exposure and subsequent lung injury,” Dr. Antony said.