Disruption of ET-1 gene enhances pulmonary responses  to methacholine via functional mechanism in knockout mice

Nagase, Takahide; Kurihara, Hiroki; Kurihara, Yukiko; Aoki-Nagase, Tomoko; Nagai, Ryozo; Ouchi, Yasuyoshi

doi:10.1152/jappl.1999.87.6.2020

Cited by 10 publications

(4 citation statements)

References 37 publications

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“…Transgenic mice with lung-specific over-expression of the human EDN1 gene develop, on the other hand, chronic lung inflammation and fibrosis [108]. Edn1 heterozygous knockout mice also show increased bronchial responsiveness and these result link EDN1 functionally to asthma and obstructive diseases [72]. To date, three studies report significant association between EDN1 and asthma [41,109,110].…”

Section: Discussionmentioning

confidence: 99%

Expression analysis of asthma candidate genes during human and murine lung development

et al. 2011

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BackgroundLittle is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function.ObjectiveTo investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma.MethodsAsthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6.ResultsIn total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. NOD1, EDN1, CCL5, RORA and HLA-G. Among the asthma genes identified in genome wide association studies, ROBO1, RORA, HLA-DQB1, IL2RB and PDE10A were differentially expressed during human lung development.ConclusionsOur data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.

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Section: Discussionmentioning

confidence: 99%

Expression analysis of asthma candidate genes during human and murine lung development

et al. 2011

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“…Transgenic mice with lungspecific over-expression of the human EDN1 gene develop, on the other hand, chronic lung inflammation and fibrosis [108]. Edn1 heterozygous knockout mice also show increased bronchial responsiveness and these result link EDN1 functionally to asthma and obstructive diseases [72]. To date, three studies report significant association between EDN1 and asthma [41,109,110].…”

Section: Discussionmentioning

confidence: 99%

Expression Analysis Of Asthma Candidate Genes During Human And Murine Lung Development

Kho

Sharma

Gaedigk

et al. 2011

C27. Genetic Programs Driving Lung Development and Regeneration

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“…ETA mediated bronchoconstriction may also be important following ETB receptor desensitization or denudation of the airway epithelium, as may occur during airway inflammation and during the late, sustained airway response to inhaled antigens [31,34,35]. Interestingly, heterozygous ET-1 knockout mice, with a 50% reduction in ET-1 peptide, have airway hyperresponsiveness but not remodeling, suggesting the decrease in ET-1 modulates bronchoconstriction activity by a functional mechanism, possibly by decreasing basal NO production [36,37]. …”

Section: Airway Diseasesmentioning

confidence: 99%

Role of endothelin-1 in lung disease

2001

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ARDS = acute respiratory distress syndrome; BAL = bronchoalveolar lavage; BO = bronchiolitis obliterans; ECE = endothelin converting enzyme; ETA = endothelin A; ETB = endothelin B; ET-1 = endothelin-1; FEV1 = forced expiratory volume in 1 s; NO = nitric oxide.Available online http://respiratory-research.com/content/2/2/090 Introduction ET-1, ET-2, and ET-3 are members of a peptide family that has been the subject of much interest in the past decade. Our laboratory and that of Highsmith identified this peptide vasoconstrictor secreted from endothelial cells [1][2][3] that was subsequently isolated, sequenced, cloned, and named by Yanagisawa in 1988 [4]. The many diverse and overlapping functions of these peptides have since implicated endothelins in both homeostatic mechanisms as well as diseases of the lungs. This review will focus on the role of endothelins (particularly ET-1), emphasizing the need to better understand endothelin biology and function in a wide variety of disorders including diseases of the airways and pulmonary vasculature, lung tumors, the acute respiratory distress syndrome, and fibrotic diseases (Table 1). Endothelin biochemistryThe endothelins are a family of 21 amino acid peptides, of which there are three distinct isoforms (ET-1, ET-2, and ET-3). The isoforms ET-2 and ET-3 differ from ET-1 by two and six amino acids, respectively, and share significant homology, especially at the carboxy terminus with sarafotoxins a-e (Fig. 1). Endothelin-1 is the most abundant isoform and has been best characterized. The lung has the highest levels of ET-1 secreted by endothelium, smooth muscle, airway epithelium, and a variety of other cells (Table 2). ET-1 also circulates in the plasma. In the normal lung, ET-1 mainly localizes to vascular endothelium, airway and vascular smooth muscle cells and, to a lesser degree, the epithelium. ET-2 has similar biologic functions as ET-1 and is found in the myocardium, kidney and placental tissues. ET-3 also circulates in plasma and is found in the central nervous system, gastrointestinal tract, lung, and kidney although the cellular source is not clear. The gene for ET-1 is located on chromosome 6, that for ET-2 on chromosome 1, and the gene for ET-3 on chromosome 20 [5].All three endothelins are synthesized as preprohormones and post-translationally processed to active peptides. ET-1 processing has been best characterized and begins with the 212 amino acid peptide (preproET-1), which is then proteolytically cleaved by endopeptidases to big ET-1 Review Role of endothelin-1 in lung disease AbstractEndothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.

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Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice

Cited by 10 publications

References 37 publications

Expression analysis of asthma candidate genes during human and murine lung development

Expression analysis of asthma candidate genes during human and murine lung development

Expression Analysis Of Asthma Candidate Genes During Human And Murine Lung Development

Role of endothelin-1 in lung disease

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