title: Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats.
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.
authors.affiliation: Department of Respiratory Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province 250021, People's Republic of China.
authors.forename: Yun-Yan
authors.initials: YY
authors.lastname: Wan
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Tian
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Guo
authors.forename: Yan-Meng
authors.initials: YM
authors.lastname: Kang
authors.forename: Zhou-Hong
authors.initials: ZH
authors.lastname: Yao
authors.forename: Xi-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
authors.forename: Dian-Jie
authors.initials: DJ
authors.lastname: Lin
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D001761:Bleomycin; D004195:Disease Models, Animal; D043169:Endostatins / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; D043169:Endostatins; D001761:Bleomycin