Hydroxypropyl Cyclodextrin Improves Amiodarone-induced Aberrant Lipid Homeostasis of Alveolar Cells
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), a cyclic oligosaccharide, 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.
| Errataetall: |
CommentIn: Am J Respir Cell Mol Biol. 2021 Apr;64(4):405-406. - PMID 33596392 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:64 |
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| Enthalten in: |
American journal of respiratory cell and molecular biology - 64(2021), 4 vom: 15. Apr., Seite 504-514 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kanagaki, Shuhei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.05.2021 Date Revised 10.05.2021 published: Print CommentIn: Am J Respir Cell Mol Biol. 2021 Apr;64(4):405-406. - PMID 33596392 Citation Status MEDLINE |
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| doi: |
10.1165/rcmb.2020-0119OC |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320554694 |
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| 520 | |a 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), a cyclic oligosaccharide, 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 | ||
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| 700 | 1 | |a Moriguchi, Keita |e verfasserin |4 aut | |
| 700 | 1 | |a Nakao, Kazuhisa |e verfasserin |4 aut | |
| 700 | 1 | |a Toyomoto, Masayasu |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Murakami, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Hagiwara, Masatoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Gotoh, Shimpei |e verfasserin |4 aut | |
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