Journal ArticleDOI
Elevated expression of endothelin-1 and endothelin-converting enzyme-1 in idiopathic pulmonary fibrosis: possible involvement of proinflammatory cytokines.
Dina Saleh,Kanako Furukawa,Ming-Sound Tsao,Azzam A. Maghazachi,Bryan Corrin,Masashi Yanagisawa,Peter J. Barnes,Adel Giaid +7 more
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TLDR
It is demonstrated that the colocalization of the precursor and active ET-1, and ECE-1 in the same cell, and that E CE-1 expression is elevated in IPF, may be mediated by proinflammatory cytokines.Abstract:
Endothelin-1 (ET-1) is a vasoconstrictor, bronchoconstrictor, and mitogenic peptide which is enzymatically converted from a biologically inactive big ET to mature ET (21 amino acid) by the ET-converting enzyme (ECE). Here, we investigate the expression of ECE-1, big ET-1, and ET-1 in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and compare it to those of normal subjects using immunohistochemistry and in situ hybridization. In normal lungs, focal moderate expression of all three molecules is localized to airway epithelium, pulmonary endothelium, and airway and vascular smooth muscle cells. Serous bronchial glands also expressed ET-1 and ECE-1. In IPF, strong diffuse expression of ECE-1 was seen in airway epithelium, proliferating type II pneumocytes, and in endothelial and inflammatory cells. ECE-1 immunostaining was colocalized to big ET-1 and ET-1 immunostaining, and correlated with disease activity (P < 0.05). To study regulatory mechanisms of ET-1 and ECE-1 expression, human normal bronchial epithelial (NBE) cells were treated with cytokines and analyzed by radioimmunoassay and Northern blot. Incubation of human NBE cells with IL-1alpha and -beta or tumor necrosis factor alpha (TNFalpha) resulted in a significant increase in ET-1 release and mRNA expression. TNFalpha resulted in a significant increase in ECE-1 mRNA expression. These findings demonstrated the colocalization of the precursor and active ET-1, and ECE-1 in the same cell, and that ECE-1 expression is elevated in IPF. In addition, increased expression of ET-1 and ECE-1 in IPF may be mediated by proinflammatory cytokines.read more
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Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.
Richard N. Channick,Gérald Simonneau,Olivier Sitbon,Ivan M. Robbins,Adaani E. Frost,Victor F. Tapson,David B. Badesch,Sébastien Roux,Maurizio Rainisio,Frédéric Bodin,Lewis J. Rubin +10 more
TL;DR: Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.
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Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling.
Sergio Rey,Gregg L. Semenza +1 more
TL;DR: This review will focus on the pivotal role of HIF-1 in vascular homeostasis, the involvement in vascular diseases, and recent advances in targeting Hif-1 for therapy in preclinical models.
Journal ArticleDOI
Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. an integral model.
Moisés Selman,Annie Pardo +1 more
TL;DR: An integral model is proposed in which the combination of some gene variants and/or gene expression in the aging lung results in the loss of epithelial integrity and consequently in the failure of the alveoli to correctly respond to injury and to face the stress associated with mechanical stretch.
Journal ArticleDOI
Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions.
TL;DR: The aim of this paper is to review the specific characteristics of BLM-induced lung fibrosis in different animal models and to summarize modalities and timing of in vivo drug administration.
Journal ArticleDOI
Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease
TL;DR: Current and emerging therapies for IPF, particularly those targeting age-related mechanisms, are discussed, and future therapeutic approaches are discussed.
References
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Journal ArticleDOI
Genomic sequencing
George M. Church,Walter Gilbert +1 more
TL;DR: The genomic sequencing procedures are applicable to the analysis of genetic polymorphisms, DNA methylation at deoxycytidines, and nucleic acid-protein interactions at single nucleotide resolution.
Journal ArticleDOI
Expression of Endothelin-1 in the Lungs of Patients with Pulmonary Hypertension
Adel Giaid,Masashi Yanagisawa,David Langleben,René P. Michel,Robert D. Levy,Hani Shennib,Sadao Kimura,Tomoh Masaki,William P. Duguid,Duncan J. Stewart +9 more
TL;DR: Preliminary results suggest that pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endethelin- 1 may contribute to the vascular abnormalities associated with this disorder.
Journal ArticleDOI
ECE-1: A membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1
Dong Xu,Noriaki Emoto,Adel Giaid,Clive A. Slaughter,Semiko Kaw,Damiane deWit,Masashi Yanagisawa +6 more
TL;DR: The identification of ECE-1 is reported, a novel membrane-bound neutral metalloprotease that is expressed abundantly in endothelial cells in vivo and is structurally related to neutral endopeptidase 24.11 and Kell blood group protein.
Journal ArticleDOI
Endothelin-converting Enzyme-2 Is a Membrane-bound, Phosphoramidon-sensitive Metalloprotease with Acidic pH Optimum (∗)
Noriaki Emoto,Masashi Yanagisawa +1 more
TL;DR: The findings suggest that ECE-2 acts as an intracellular enzyme responsible for the conversion of endogenously synthesized big ET-1 at the trans-Golgi network, where the vesicular fluid is acidified.
Journal ArticleDOI
Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis. A mouse model of progressive pulmonary fibrosis
Yoshitaka Miyazaki,Kimi Araki,Christian Vesin,Irène Garcia,Yusuf Kapanci,Jeffrey A. Whitsett,Pierre F. Piguet,Pierre Vassalli +7 more
TL;DR: Pulmonary pathology in the SP-C T NF-alpha mice bears a striking resemblance to human idiopathic pulmonary fibrosis, in which increased expression of TNF-alpha in type II epithelial cells has also been noted.
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