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

Respiratory Research

Dian-Jie Lin³  Qing-Hua Liu³  Xi-Li Li³  Zhou-Hong Yao³  Yan-Meng Kang³  Hai-Sheng Guo²  Guang-Yan Tian¹  Yun-Yan Wan³ 

[1] Department of Neurology, Jinan Children's Hospital, Jinan, Shandong Province 250021, People's Republic of China;Department of Respiratory Medicine, Dongying People's Hospital, Dongying, Shandong Province 257000, People's Republic of China;Department of Respiratory Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province 250021, People's Republic of China

关键词: Epithelial cell apoptosis;    Inflammation;    Extracellular signal-regulated protein kinase 1/2;    Vascular endothelial growth factor;    Angiogenesis;    Pulmonary fibrosis;    Bleomycin;    Endostatin;   

Others  :  794609
DOI  :  10.1186/1465-9921-14-56

 received in 2013-01-06, accepted in 2013-05-15,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Wan et al.; licensee BioMed Central Ltd.

【 图 表 】

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