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Changes in factor VII-activating protease in a bleomycin-induced lung injury rat model and its influence on human pulmonary fibroblasts in vitro

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by non-cardiogenic pulmonary edema, respiratory distress and hypoxemia. Factor VII-activating protease (FSAP) is a plasma-derived protease which inhibits the proliferation and migration of hepatic stellate cells and vascular smooth muscle cells. This study was designed to determine the dynamic expression changes in FSAP in a bleomycin-induced pulmonary fibrosis rat model and the influence of FSAP on human pulmonary fibroblasts (HPF). The expression of FSAP was examined in a rat model of bleomycin-induced pulmonary fibrosis by immunohistochemical staining, quantitative real-time RT-PCR and Western blot analysis. The influence of FSAP on cell proliferation and migration of HPF was investigated by the BrdU incorporation assay and transwell cell culture chambers, respectively. The effect of FSAP on platelet-derived growth factor (PDGF)-stimulated p42/p44 mitogen-activated protein kinase (MAPK) activation on HPF was determined by Western blot analysis. FSAP was observed prominently in alveolar epithelial cells as well as microvascular endothelial cells of the lung parenchyma and was markedly increased at the early phase of bleomycin-induced pulmonary fibrosis, but decreased at the late stage, particularly during the pulmonary fibrosis. FSAP inhibited PDGF-stimulated proliferation, migration, p42/p44 MAPK phosphorylation and collagen III synthesis of the HPF. We concluded that epithelial cells in lungs represent a source of FSAP at the early stage in acutely injured lung. Moreover, we demonstrated an inhibitory effect of FSAP on PDGF-stimulated proliferation and migration of HPF in vitro, suggesting that FSAP may modulate inflammation and exert a beneficial effect on ARDS.
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Document Type: Research Article

Affiliations: Department of Intensive Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China

Publication date: October 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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