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Open Access 01-12-2018 | Research

Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis

Authors: Shinpei Kato, Naoki Inui, Akio Hakamata, Yuzo Suzuki, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Hiroshi Watanabe, Takafumi Suda

Published in: Respiratory Research | Issue 1/2018

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.

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Title: Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis
Authors: Shinpei Kato
Naoki Inui
Akio Hakamata
Yuzo Suzuki
Noriyuki Enomoto
Tomoyuki Fujisawa
Yutaro Nakamura
Hiroshi Watanabe
Takafumi Suda
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-018-0831-y

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Changes in pulmonary endothelial cell properties during bleomycin-induced pulmonary fibrosis

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