A murine model of acute lung injury identifies growth factors to promote tissue repair and their biomarkers
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- Takeyuki Kurosawa
- Department of Biochemistry Toho University Graduate School of Medicine Tokyo Japan
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- Shion Miyoshi
- Department of Biochemistry Toho University Graduate School of Medicine Tokyo Japan
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- Soh Yamazaki
- Department of Biochemistry Toho University Graduate School of Medicine Tokyo Japan
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- Takashi Nishina
- Department of Biochemistry Toho University Graduate School of Medicine Tokyo Japan
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- Tetuo Mikami
- Department of Pathology Toho University Graduate School of Medicine Tokyo Japan
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- Akira Oikawa
- RIKEN Center for Sustainable Resource Science Yokohama Japan
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- Sakae Homma
- Department of Respiratory Medicine Toho University Graduate School of Medicine Tokyo Japan
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- Hiroyasu Nakano
- Department of Biochemistry Toho University Graduate School of Medicine Tokyo Japan
Abstract
<jats:title>Abstract</jats:title><jats:p>Type II alveolar epithelial cells (AEC2s) play a crucial role in the regeneration of type I AECs after acute lung injury. The mechanisms underlying the regeneration of AEC2s are not fully understood. To address this issue, here, we investigated a murine model of acute lung injury using mice expressing human <jats:italic>Diphtheria Toxin Receptor (DTR)</jats:italic> under the control of <jats:italic>Lysozyme M</jats:italic> promoter (<jats:italic>LysM‐DTR)</jats:italic>. DT injection induced the depletion of AEC2s, alveolar macrophages, and bone marrow (BM)‐derived myeloid cells in <jats:italic>LysM‐DTR</jats:italic> mice, and the mice died within 6 days after DT injection. Apoptotic AEC2s and bronchiolar epithelial cells appeared at 24 hr, whereas Ki67‐positive proliferating cells appeared in the alveoli and bronchioles in the lung of <jats:italic>LysM‐DTR</jats:italic> mice at 72–96 hr after DT injection. Transfer of wild‐type BM cells into <jats:italic>LysM‐DTR</jats:italic> mice accelerated the regeneration of AEC2s along with the up‐regulation of several growth factors. Moreover, several metabolites were significantly decreased in the sera of <jats:italic>LysM‐DTR</jats:italic> mice compared with WT mice after DT injection, suggesting that these metabolites might be biomarkers to predict AEC2s injury. Together, <jats:italic>LysM‐DTR</jats:italic> mice might be useful to identify growth factors to promote lung repair and the metabolites to predict the severity of lung injury.</jats:p>
Journal
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- Genes to Cells
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Genes to Cells 24 (2), 112-125, 2018-12-18
Wiley
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Keywords
Details 詳細情報について
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- CRID
- 1360004235522452480
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- ISSN
- 13652443
- 13569597
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- Data Source
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- Crossref
- KAKEN