Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis
Abstract Background 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. Methods We isolated pulmonary endothelial cells, using a mag...
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doaj-6086ba14c3164caa83f4c47b2a97471c2020-11-24T20:57:47ZengBMCRespiratory Research1465-993X2018-06-0119111210.1186/s12931-018-0831-yChanges in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosisShinpei Kato0Naoki Inui1Akio Hakamata2Yuzo Suzuki3Noriyuki Enomoto4Tomoyuki Fujisawa5Yutaro Nakamura6Hiroshi Watanabe7Takafumi Suda8Second Division, Department of Internal Medicine, Hamamatsu University School of MedicineSecond Division, Department of Internal Medicine, Hamamatsu University School of MedicineDepartment of Clinical Pharmacology and Therapeutics, Hamamatsu University School of MedicineSecond Division, Department of Internal Medicine, Hamamatsu University School of MedicineSecond Division, Department of Internal Medicine, Hamamatsu University School of MedicineSecond Division, Department of Internal Medicine, Hamamatsu University School of MedicineSecond Division, Department of Internal Medicine, Hamamatsu University School of MedicineDepartment of Clinical Pharmacology and Therapeutics, Hamamatsu University School of MedicineSecond Division, Department of Internal Medicine, Hamamatsu University School of MedicineAbstract Background 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. Methods 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. Results 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. Conclusion Bleomycin administration induced functional changes in lung endothelial cells, indicating potential involvement of endothelium in pulmonary fibrogenesis.http://link.springer.com/article/10.1186/s12931-018-0831-yα-SMABleomycinEndothelial cellFibrosisNitric oxideProstaglandin I2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shinpei Kato Naoki Inui Akio Hakamata Yuzo Suzuki Noriyuki Enomoto Tomoyuki Fujisawa Yutaro Nakamura Hiroshi Watanabe Takafumi Suda |
spellingShingle |
Shinpei Kato Naoki Inui Akio Hakamata Yuzo Suzuki Noriyuki Enomoto Tomoyuki Fujisawa Yutaro Nakamura Hiroshi Watanabe Takafumi Suda Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis Respiratory Research α-SMA Bleomycin Endothelial cell Fibrosis Nitric oxide Prostaglandin I2 |
author_facet |
Shinpei Kato Naoki Inui Akio Hakamata Yuzo Suzuki Noriyuki Enomoto Tomoyuki Fujisawa Yutaro Nakamura Hiroshi Watanabe Takafumi Suda |
author_sort |
Shinpei Kato |
title |
Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis |
title_short |
Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis |
title_full |
Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis |
title_fullStr |
Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis |
title_full_unstemmed |
Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis |
title_sort |
changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2018-06-01 |
description |
Abstract Background 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. Methods 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. Results 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. Conclusion Bleomycin administration induced functional changes in lung endothelial cells, indicating potential involvement of endothelium in pulmonary fibrogenesis. |
topic |
α-SMA Bleomycin Endothelial cell Fibrosis Nitric oxide Prostaglandin I2 |
url |
http://link.springer.com/article/10.1186/s12931-018-0831-y |
work_keys_str_mv |
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