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Respiratory Research
Published in: Respiratory Research 1/2013

Open Access 01-12-2013 | Research

Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats

Authors: Yun-Yan Wan, Guang-Yan Tian, Hai-Sheng Guo, Yan-Meng Kang, Zhou-Hong Yao, Xi-Li Li, Qing-Hua Liu, Dian-Jie Lin

Published in: Respiratory Research | Issue 1/2013

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Abstract

Background

Recent evidence has demonstrated the role of angiogenesis in the pathogenesis of pulmonary fibrosis. Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis. The aim of our study was to assess whether endostatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in rats.

Methods

The rats were randomly divided into five experimental groups: (A) saline only, (B) BLM only, (C) BLM plus early endostatin treatment, (D) BLM plus late endostatin treatment, and (F) BLM plus whole-course endostatin treatment. We investigated the microvascular density (MVD), inflammatory response and alveolar epithelial cell apoptosis in rat lungs in each group at different phases of disease development.

Results

Early endostatin administration attenuated fibrotic changes in BLM-induced pulmonary fibrosis in rats. Endostatin treatment decreased MVD by inhibiting the expression of VEGF/VEGFR-2 (Flk-1) and the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). Endostatin treatment also decreased the number of inflammatory cells infiltrating the bronchoalveolar lavage fluid during the early inflammatory phase of BLM-induced pulmonary fibrosis. In addition, the levels of tumour necrosis factor-α (TNF-α) and transforming growth factor β1 (TGF-β1) were reduced by endostatin treatment. Furthermore, endostatin decreased alveolar type II cell apoptosis and had an epithelium-protective effect. These might be the mechanism underlying the preventive effect of endostatin on pulmonary fibrosis.

Conclusions

Our findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.
Appendix
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Metadata
Title
Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats
Authors
Yun-Yan Wan
Guang-Yan Tian
Hai-Sheng Guo
Yan-Meng Kang
Zhou-Hong Yao
Xi-Li Li
Qing-Hua Liu
Dian-Jie Lin
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2013
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-14-56

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