Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis.
Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis.
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DOI：
10.1186/s12931-018-0831-y
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发表时间：
2018-06-26
影响因子：
5.8
通讯作者：
Suda T
中科院分区：
文献类型：
--
作者：
Kato S;Inui N;Hakamata A;Suzuki Y;Enomoto N;Fujisawa T;Nakamura Y;Watanabe H;Suda T
肺纤维化是一种进行性和致命性疾病，其特征是肺实质受损，细胞外基质过度沉积。内皮细胞在纤维化发展中的作用尚不清楚。我们使用磁激活细胞分选系统从气管内注射博莱霉素诱导的肺纤维化小鼠中分离出肺内皮细胞。我们对肺纤维化发展过程中不同时间分离的内皮细胞进行了表征。博莱霉素组在给药后7d可见炎性细胞浸润，第21天可见纤维化改变，胶原含量增加。在这两个时间点分离内皮细胞。在博莱霉素处理的小鼠肺内皮细胞中，von Willebrand因子、纤溶酶原激活物抑制物-1和基质金属蛋白酶-12的水平在第7天和第21天升高。提示气管内注射博莱霉素可致血管内皮损伤。与未处理组相比，博莱霉素组肺组织纤维化介质、转化生长因子-β、结缔组织生长因子和血小板衍化生长因子-C的表达增加。当用转化生长因子-β，α处理内皮细胞时，只有博莱霉素处理的小鼠肺内皮细胞的平滑肌肌动蛋白表达和胶原生成增加。转化生长因子-β可进一步抑制博莱霉素组小鼠肺内皮细胞前列腺素I2和一氧化氮的生成。博莱霉素可引起肺内皮细胞功能改变，提示内皮细胞可能参与了肺纤维化的形成。本文的在线版本(10.1186/s12931-0180831-y)包含向授权用户提供的补充材料。
Pulmonary fibrosis is a progressive and lethal disease characterized by damage to the lung parenchyma with excess extracellular matrix deposition. The involvement of endothelial cells in fibrosis development is unclear. We isolated pulmonary endothelial cells, using a magnetic-activated cell sorting system, from mice with pulmonary fibrosis induced by intratracheal bleomycin. We characterized endothelial cells isolated at various times in the course of pulmonary fibrosis development. Inflammatory cell infiltration was observed at 7 days after bleomycin administration, and fibrotic changes with increased collagen content were observed on day 21. Endothelial cells were isolated at these two timepoints. Levels of von Willebrand factor, plasminogen activator inhibitor-1 and matrix metalloproteinase-12 were elevated in lung endothelial cells isolated from bleomycin-treated mice at days 7 and 21. This indicated that intratracheal bleomycin administration induced endothelium injury. Expression of fibrogenic mediators, transforming growth factor (TGF)-β, connective tissue growth factor and platelet-derived growth factor-C was elevated in the cells from bleomycin-treated, compared with untreated, lungs. When endothelial cells were treated with TGF-β, α-smooth muscle actin (SMA) expression and collagen production were increased only in those cells from bleomycin-treated mouse lungs. Thapsigargin-induced prostaglandin I2 and nitric oxide production, decreased in endothelial cells from bleomycin-treated mouse lungs, compared with controls, was further suppressed by TGF-β. Bleomycin administration induced functional changes in lung endothelial cells, indicating potential involvement of endothelium in pulmonary fibrogenesis. The online version of this article (10.1186/s12931-018-0831-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1165/rcmb.2013-0152oc
发表时间：
2013-12-01
影响因子：
6.4
作者：
Leach, Heather G.;Chrobak, Izabela;Trojanowska, Maria
通讯作者：
Trojanowska, Maria
DOI：
10.1164/rccm.200907-1164oc
发表时间：
2010-08-01
影响因子：
24.7
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通讯作者：
Soler, Paul
DOI：
10.1165/ajrcmb/5.2.155
发表时间：
1991-08-01
影响因子：
6.4
作者：
KHALIL, N;OCONNOR, RN;GREENBERG, AH
通讯作者：
GREENBERG, AH
DOI：
10.1186/1755-1536-6-15
发表时间：
2013-08-08
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Akamatsu T;Arai Y;Kosugi I;Kawasaki H;Meguro S;Sakao M;Shibata K;Suda T;Chida K;Iwashita T
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Iwashita T
DOI：
10.1165/rcmb.2008-0182oc
发表时间：
2009-12
影响因子：
6.4
作者：
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