Analysis of molecular mechanism of drug-induced lung fibrosis and development of strategy to predict and prevent the fibrosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293033
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: Takano Mikihisa 広島大学, 医歯薬保健学研究科(薬), 教授 (20211336)
• Co-Investigator(Renkei-kenkyūsha): YUMOTO Ryoko 広島大学, 大学院医歯薬保健学研究科, 准教授 (70379915) ; KAWAMI Masashi 広島大学, 大学院医歯薬保健学研究科, 助教 (20725775)
• Research Collaborator: Ehrhardt Carsten ; Kim Kwang-Jin
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 薬剤性肺線維症 / 肺胞上皮Ⅱ型細胞 / 上皮間葉転換 / メトトレキサート / ブレオマイシン / マイクロRNA / ケルセチン

Outline of Final Research Achievements

Mechanisms underlying drug-induced pulmonary injury were investigated from the viewpoint of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells deeply related to pulmonary fibrosis. We have found that (1) drugs such as methotrexate act directly on alveolar epithelial cells to cause EMT, (2) various factors such as Smad2 phosphorylation, extracellular secretion factor, and microRNA are involved in the induction of EMT by drugs, (3) quercetin which is used as a supplement in Japan has been shown to have EMT inhibitory effect. These findings would be useful for understanding the molecular mechanisms of drug-induced lung injury and developing strategies for preventing pulmonary disorders.

Free Research Field

生物薬剤学