2026-03-06T14:51:01Z https://hama-med.repo.nii.ac.jp/oai

oai:hama-med.repo.nii.ac.jp:02000106 2024-03-15T02:53:32Z 2:15:17

ブレオマイシン誘導性肺線維症モデルマウスの肺血管内皮細胞に対する低酸素の影響 Effect of hypoxia on pulmonary endothelial cells from bleomycin-induced pulmonary fibrosis model mice 赤堀, 大介 アカホリ, ダイスケ Akahori, Daisuke α-SMA bleomycin endothelial cell hypoxia HIF-α pulmonary fibrosis 浜松医科大学 博士（医学） dotoral 医学系研究科 Pulmonary fibrosis is a progressive and fatal disorder characterized by dysregulated repair after recurrent injury. Destruction of the lung architecture with excess extracellular matrix deposition induces respiratory failure with hypoxia and progressive dyspnea. The impact of hypoxia on pulmonary endothelial cells during pulmonary fibrogenesis is unclear. Using a magnetic-activated cell sorting system, pulmonary endothelial cells were isolated from a mouse model of pulmonary fibrosis induced by intratracheally administered bleomycin. When endothelial cells were exposed to hypoxic conditions, a hypoxia-inducible factor (HIF)-2α protein was detected in CD31- and α-smooth muscle actin (SMA)-positive cells. Levels of plasminogen activator inhibitor 1, von Willebrand factor, and matrix metalloproteinase 12 were increased in endothelial cells isolated from bleomycin-treated mice exposed to hypoxic conditions. When endothelial cells were cultured under hypoxic conditions, levels of fibrotic mediators, transforming growth factor- and connective tissue growth factor, were elevated only in endothelial cells from bleomycin-treated and not from saline-treated lungs. The increased expression of α-SMA and mesenchymal markers and collagen production in bleomycin- or hypoxia-stimulated endothelial cells were further elevated in endothelial cells from bleomycin-treated mouse lungs cultured under hypoxic conditions. Exposure to hypoxia damaged endothelial cells and enhanced fibrogenesis-related damage in bleomycin-treated pulmonary endothelial cells. doctoral thesis MDPI (Multidisciplinary Digital Publishing Institute) 2022-08-12 2023-03-16 VoR application/pdf International Journal of Molecular Sciences 16 23 8996 甲第929号 1422-0067 AA12038549 https://hama-med.repo.nii.ac.jp/record/2000106/files/DT_929ronbun.pdf http://hdl.handle.net/10271/0002000106 https://hama-med.repo.nii.ac.jp/records/2000106 eng 36012260 https://doi.org/10.3390/ijms23168996 (C) 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). open access