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- 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; Wan, Yun-Yan; Tian, Guang-Yan; Guo, Hai-Sheng; Kang, Yan-Meng; Yao, Zhou-Hong; Li, Xi-Li; Liu, Qing-Hua; Lin, Dian-Jie
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Our findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.
- Subjects
ENDOSTATIN; BLEOMYCIN; PULMONARY fibrosis; NEOVASCULARIZATION; LABORATORY rats; VASCULAR endothelial growth factors; EXTRACELLULAR signal-regulated kinases; COLLAGEN; GROWTH factors; ANIMAL experimentation; BIOLOGICAL models; COMPARATIVE studies; RESEARCH methodology; MEDICAL cooperation; RATS; RESEARCH; EVALUATION research; TREATMENT effectiveness; THERAPEUTICS
- Publication
Respiratory Research, 2013, Vol 14, Issue 5, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/1465-9921-14-56