Development of a novel model of alveolar type I cells for the study on drug transport and toxicity in the lung

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670078
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: TAKANO MIKIHISA 広島大学, 医歯薬保健学研究院(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院, 准教授 (70379915)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬学 / 肺胞上皮細胞 / Ⅰ型細胞 / モデル細胞開発 / 分化転換

Outline of Final Research Achievements

The distal air spaces of the lungs are lined with a continuous epithelium comprising two types of alveolar epithelial cells, type I and type II. At present, no good cell line having type I cell-like phenotype is available. In alveolar epithelial cells, P-glycoprotein (P-gp) is selectively expressed in type I cells but not in type II cells. Using a limited dilution method, we successfully isolated an A549 clone (A549/P-gp) highly expressing P-gp as well as type I cell marker mRNAs, while P-gp expression in native A549 cells was negligible. Using A549/P-gp cells, the effect of cigarette smoke extract (CSE) on P-gp function in the lung alveoli was examined, and we found that CSE had inhibitory effect on P-gp function. A549/P-gp cells would be useful as a novel model of alveolar type I cells.

Free Research Field

生物薬剤学