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Role of endothelin-1 and endothelin converting enzyme-1 in bleomycin-induced pulmonary fibrosis in rats

Idiopathic pulmonary fibrosis (IPF) belongs to the group of the interstitial lung diseases and is characterized by inflammation, proliferation of fibroblasts and type II pneumocytes, and increased collagen deposition. Inflammatory cells, by releasing mediators and cytokines, participate in the pathogenesis of IPF. Endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide, is one of the mediators that has been shown to be involved in the fibrotic process of IPF in humans. There are, however, no studies examining the role of ET-1 in animal models of IPF. We used the rat model of pulmonary fibrosis, induced by bleomycin, to study the role of ET-1 and endothelin converting enzyme-1 (ECE-1) in IPF using immunohistochemistry (IHC). We also studied by morphometry the effect of bosentan, the mixed ET-A/B receptor antagonist, on the severity of the fibrosis. We found increased ET-1 and ECE-1 immunoreactivities in the lungs of the fibrosis group compared with the control group (P $<$ 0.05), principally in epithelial cells. By morphometry, we found a decrease in the volume fraction (Vv) of air and an increase in the Vv of connective tissue in the fibrosis group compared with control. The fibrosis was significantly reduced by bosentan (P $<$ 0.05). These results are consistent with the notion that ET-1 is an important mediator of bleomycin-induced pulmonary fibrosis.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.24032
Date January 1996
CreatorsPark, Sung-Hae, 1971-
ContributorsMichel, Rene P. (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Pathology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001529684, proquestno: MM19842, Theses scanned by UMI/ProQuest.

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