CD as Drug: Hydroxypropyl Cyclodextrin Improves Amiodarone-induced Aberrant Lipid Homeostasis of Alveolar Cells

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Alveolar epithelial type II (AT2) cells secrete pulmonary surfactant via lamellar bodies (LBs). Abnormalities in LBs are associated with pulmonary disorders, including fibrosis. However, high-content screening (HCS) for LB abnormalities is limited by the lack of understanding of AT2 cell functions. In the present study, we have developed LB cells harboring LB-like organelles that secrete surfactant proteins. These cells were more similar to AT2 cells than to parental A549 cells. LB cells recapitulated amiodarone (AMD)-induced LB enlargement, similar to AT2 cells of patients exposed to AMD. To reverse AMD-induced LB abnormalities, we performed HCS of approved drugs and identified 2-hydroxypropyl-β-cyclodextrin (HPβCD), as a potential therapeutic agent. A transcriptome analysis revealed that HPβCD modulates lipid homeostasis. In addition, HPβCD inhibited AMD-induced LB abnormalities in human induced pluripotent stem cell–derived AT2 cells. Our results demonstrate that LB cells are useful for HCS and suggest that HPβCD is a candidate therapeutic agent for AMD-induced interstitial pneumonia.

Kanagaki, S., Suezawa, T., Moriguchi, K., (...), Hagiwara, M., Gotoh, S. (2021)  Hydroxypropyl cyclodextrin improves amiodarone-induced aberrant lipid homeostasis of alveolar cells.  American Journal of Respiratory Cell and Molecular Biology 64, 504-514.  

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