Preventive approach against drug-induced pulmonary fibrosis through the suppression of epithelial-mesenchymal transition

Abstract

A number of drugs induce pulmonary injury and subsequently lead to serious lung diseases such as pulmonary fibrosis as the adverse drug reactions. However, an effective preventive approach against drug-induced pulmonary fibrosis has not been established due to poor understanding of common preventive targets in a variety of drugs showing pulmonary toxicity. Epithelial-mesenchymal transition (EMT), a cellular phenotypic change of the epithelial to mesenchymal state, contributes to the development of pulmonary fibrosis through the conversion of damaged alveolar epithelium into myofibroblasts. As several drugs with pulmonary toxicity have been reported to induce EMT, EMT serves as a bridge between the drugs and pulmonary fibrosis. Accumulated evidence supports the potential of EMT as a preventive target against drug-induced pulmonary fibrosis. Additionally, since there are mechanistic differences between the main pharmacological effect and EMT induced by the drug, prevention based on EMT suppression would be possible and would contribute to continuous clinical treatment with the drug to avoid EMT-mediated serious pulmonary fibrosis. Furthermore, targeting EMT seems to be adequate for exerting a preventive effect since EMT in damaged alveolar epithelial cells occurs prior to the development of the pathophysiological state of the whole lung in a bleomycin-induced lung injury rat model. This viewpoint deals with the benefits and perspectives of preventive approaches against druginduced pulmonary fibrosis through the suppression of EMT, which has rarely been addressed.