Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
[Objectives] Drug-induced lung injury (DILI) is caused by a number of pharmaceuticals, and subsequently associated with serious diseases such as pulmonary fibrosis. However, there are currently no effective diagnostic method to predict DILI at early phase. We demonstrated that several pulmonary toxic drugs induced epithelial-mesenchymal transition (EMT) associated with pulmonary fibrosis, and certain microRNAs were associated with drug-induced EMT. In this study, we aimed to identify and evaluate the microRNAs associated with EMT as effective biomarkers for predicting DILI. [Methods] BLM solution intratracheally administered into rats, and the lungs were isolated from the rats at Day 3, 7, and 14. mRNA and protein expression levels of EMT-related markers were evaluated by real-time PCR and western blot analysis, respectively. [Results and Discussion] The amounts of hydroxy proline, a fibrosis marker, in the lung was increased at Day 14, but not ad Day 7. On the other hand, EMT phenotype with decrease in epithelial markers and increase in mesenchymal markers occurred at Day 7, suggesting that EMT would occur before reaching to pulmonary fibrosis. Several microRNAs including miR-222 in plasma and bronchoalveolar lavage fluid were also upregulated, thereby these microRNAs may be effective for predicting pathophysiological changes in the lung.
