Study on the mechanism of epithelial-mesenchymal transition as a cause of drug-induced lung injury, and development of the strategy for preventing the injury

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: Ryoko Yumoto 広島大学, 医歯薬保健学研究科(薬), 准教授 (70379915)
• Co-Investigator(Renkei-kenkyūsha): TAKANO Mikihisa 広島大学, 大学院医歯薬保健学研究科, 教授 (20211336)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 薬物動態学 / 薬剤性肺障害 / 肺胞上皮細胞 / 上皮間葉転換 / TGF-β1 / quercetin

Outline of Final Research Achievements

Many drugs used in clinical pharmacotherapy often induce serious injury of the lungs and sometimes result in lethal interstitial lung diseases. Though there is a great variation in the reported values about the prevalence of drug-induced lung diseases, it is high especially in the case of bleomycin. It is now recognized that epithelial-mesenchymal transition (EMT) plays an essential role in the fibrosis of various organs and is acknowledged to be one of the mechanisms underlying the generation of mesenchymal cells participating in tissue fibrosis.
In this study, we have found that RLE/Abca3 cells is a good in-vitro model to study drug-induced EMT, and TGF-β1 would be involved in the mechanism underlying bleomycin-induced EMT. In addition, quercetin, a flavonoid, may be a good therapeutic agent for drug-induced lung injury, which inhibits the intracellular ROS production and the TGF-β/smad pathway.

Free Research Field

薬剤学