Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats. Academic Article uri icon

Overview

MeSH

  • Animals
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

MeSH Major

  • Angiogenesis Inducing Agents
  • Bleomycin
  • Disease Models, Animal
  • Endostatins
  • Pulmonary Fibrosis

abstract

  • 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. 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. 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. Our findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.

publication date

  • 2013

has subject area

  • Angiogenesis Inducing Agents
  • Animals
  • Bleomycin
  • Disease Models, Animal
  • Endostatins
  • Humans
  • Male
  • Pulmonary Fibrosis
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3668162

Digital Object Identifier (DOI)

  • 10.1186/1465-9921-14-56

PubMed ID

  • 23688086

Additional Document Info

start page

  • 56

volume

  • 14

number

  • 1