Hydroxypropyl Cyclodextrin Improves Amiodarone-induced Aberrant Lipid Homeostasis of Alveolar Cells.
Am J Respir Cell Mol Biol
; 64(4): 504-514, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33493427
ABSTRACT
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-ß-cyclodextrin (HPßCD), a cyclic oligosaccharide, as a potential therapeutic agent. A transcriptome analysis revealed that HPßCD modulates lipid homeostasis. In addition, HPßCD 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 HPßCD is a candidate therapeutic agent for AMD-induced interstitial pneumonia.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metabolismo dos Lipídeos
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Células Epiteliais Alveolares
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Células-Tronco Pluripotentes Induzidas
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2-Hidroxipropil-beta-Ciclodextrina
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Amiodarona
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article