Endothelial-to-mesenchymal transition in lipopolysaccharide-induced acute lung injury drives a progenitor cell-like phenotype
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- Toshio Suzuki
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Yuji Tada
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Rintaro Nishimura
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Takeshi Kawasaki
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Ayumi Sekine
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Takashi Urushibara
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Fumiaki Kato
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Taku Kinoshita
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- Jun Ikari
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
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- James West
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
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- Koichiro Tatsumi
- Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; and
書誌事項
- 公開日
- 2016-06-01
- 資源種別
- journal article
- DOI
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- 10.1152/ajplung.00074.2016
- 公開者
- American Physiological Society
この論文をさがす
説明
<jats:p>Pulmonary vascular endothelial function may be impaired by oxidative stress in endotoxemia-derived acute lung injury. Growing evidence suggests that endothelial-to-mesenchymal transition (EndMT) could play a pivotal role in various respiratory diseases; however, it remains unclear whether EndMT participates in the injury/repair process of septic acute lung injury. Here, we analyzed lipopolysaccharide (LPS)-treated mice whose total number of pulmonary vascular endothelial cells (PVECs) transiently decreased after production of reactive oxygen species (ROS), while the population of EndMT-PVECs significantly increased. NAD(P)H oxidase inhibition suppressed EndMT of PVECs. Most EndMT-PVECs derived from tissue-resident cells, not from bone marrow, as assessed by mice with chimeric bone marrow. Bromodeoxyuridine-incorporation assays revealed higher proliferation of capillary EndMT-PVECs. In addition, EndMT-PVECs strongly expressed c- kit and CD133. LPS loading to human lung microvascular endothelial cells (HMVEC-Ls) induced reversible EndMT, as evidenced by phenotypic recovery observed after removal of LPS. LPS-induced EndMT-HMVEC-Ls had increased vasculogenic ability, aldehyde dehydrogenase activity, and expression of drug resistance genes, which are also fundamental properties of progenitor cells. Taken together, our results demonstrate that LPS induces EndMT of tissue-resident PVECs during the early phase of acute lung injury, partly mediated by ROS, contributing to increased proliferation of PVECs.</jats:p>
収録刊行物
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- American Journal of Physiology-Lung Cellular and Molecular Physiology
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American Journal of Physiology-Lung Cellular and Molecular Physiology 310 (11), L1185-L1198, 2016-06-01
American Physiological Society
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キーワード
- Lipopolysaccharides
- Acute Lung Injury
- Gene Expression
- NADPH Oxidases
- Apoptosis
- Mice, Inbred C57BL
- Transforming Growth Factor beta1
- Transforming Growth Factor beta2
- Phenotype
- Cell Transdifferentiation
- Animals
- Female
- Endothelium, Vascular
- Reactive Oxygen Species
- Cells, Cultured
- Cell Proliferation
- Endothelial Progenitor Cells
詳細情報 詳細情報について
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- CRID
- 1360004236326030336
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- ISSN
- 15221504
- 10400605
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- PubMed
- 27106288
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE