Mucin Overproduction in Chronic Inflammatory Lung Disease

Hauber, Hans-Peter; Foley, Susan; Hamid, Qutayba

doi:10.1155/2006/901417

Cited by 69 publications

(48 citation statements)

References 141 publications

(162 reference statements)

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“…Airway remodeling with goblet cell metaplasia, submucosal gland hyperplasia, and mucus hypersecretion are common features of several inflammatory airways diseases, including chronic bronchitis, cystic fibrosis, and asthma (21)(22)(23). Mucus hypersecretion as a result of goblet cell hyperplasia causes airway mucus plugging, especially in the peripheral airways, where numerous large secreting goblet cells can more easily cause obstruction (24).…”

Section: Discussionmentioning

confidence: 99%

Absence of Proteinase-Activated Receptor-1 Signaling in Mice Confers Protection from fMLP-Induced Goblet Cell Metaplasia

Atzori

Lucattelli²,

Scotton³

et al. 2009

Am J Respir Cell Mol Biol

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The morphological features of chronic obstructive pulmonary disease in man include emphysema and chronic bronchitis associated with mucus hypersecretion. These alterations can be induced in mice by a single intratracheal instillation of N-formyl-L-methionyl-Lleucyl-L-phenylalanine (fMLP), a chemoattractant and degranulating agent for neutrophils. The mechanisms underlying excessive mucus production and, in particular, goblet cell hyperplasia/metaplasia in chronic obstructive pulmonary disease remain poorly understood. The proteinase-activated receptors (PARs) are widely recognized for their modulatory properties during inflammation. In this study, we examined whether PAR-1 contributes to inflammation and lung damage induced by fMLP by comparing the response of PAR-1-deficient (PAR-1 2/2 ) mice with that of wild-type (WT) mice. Mice were killed at various time points after fMLP instillation (200 mg/50 ml). WT mice developed emphysema and goblet cell metaplasia. The onset of pulmonary lesions was preceded by an increase in thrombin immunoreactivity in bronchial airways and alveolar tissue. This was followed by a decrease in PAR-1 immunoreactivity, and by an increase in IL-13 immunostaining on the luminal surface of airway epithelial cells. In PAR-1 2/2 mice, fMLP administration induced similar responses in terms of inflammation and emphysema, but these mice were protected from the development of goblet cell metaplasia. The involvement of PAR-1 in airway epithelial cell transdifferentiation was confirmed by demonstrating that intratracheal instillation of the selective PAR-1 agonist (TFLLR) induced goblet cell metaplasia in the airways of WT mice only. These data suggest that emphysema and goblet cell metaplasia occur independently, and that PAR-1 signaling through IL-13 stimulation may play an important role in inducing goblet cell metaplasia.Keywords: goblet cell metaplasia; emphysema; proteinase-activated receptor-1; IL-13; epidermal growth factor receptor Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem. Morphological features of COPD include emphysema (airspace enlargement due to destruction of the lung parenchyma) and chronic bronchitis associated with mucus hypersecretion. A central pathogenetic role in COPD has been attributed to the inflammatory response that is present throughout the airways and parenchyma, and which participates in the progression and exacerbation of this disease (1). Neutrophils and macrophages release mediators that contribute to inflammation and overwhelm lung defenses (2, 3). These mediators can injure the alveolar walls by activating program(s) for lung destruction (emphysema), and/or can remodel the airways by inducing goblet cell metaplasia (3). Although the mechanisms of hypersecretion are not fully understood, increased mucus secretion is currently attributed to hypertrophy and hyperplasia of bronchial submucosal glands and goblet cell hyperplasia/metaplasia in the airway epithelium (4). In the bronchial epithelium, the reduction of ci...

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Section: Discussionmentioning

confidence: 99%

Absence of Proteinase-Activated Receptor-1 Signaling in Mice Confers Protection from fMLP-Induced Goblet Cell Metaplasia

Atzori

Lucattelli²,

Scotton³

et al. 2009

Am J Respir Cell Mol Biol

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“…В настоя-щее время у человека идентифицировано 20 муци- [11]. Увеличение генера-ции АКМ сопровождается повышением экспрессии гена муцина и увеличением секреции муцина, в ре-зультате чего повышается уровень антиоксидантной защиты респираторного тракта.…”

Section: муковисцидозunclassified

Нозоспецифічні Особливості Редокс-Процесів При Муковісцидозі

Абатуров

Волосовец²,

Khudyakov

2021

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Резюме. В обзоре литературы изложены современные данные об особенностях редокс-процессов, проис-ходящих в просвете респираторного тракта при муковисцидозеКлючевые слова: заболевания органов дыхания; антиоксидантная система © «Здоровье ребенка», 2017

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“…Hypersecretion of mucus results from hyperplasia and metaplasia of mucous cells, which lead to greater numbers of these cells being found throughout the airways, including the distal airways, where they are normally absent [200]. The mechanisms involved in the upregulation of secreted mucins in lung cancer was studied by Hauber et al [201] and they discussed the induction of mucin by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction. Fahy et al [202] examined the normal formation and clearance of airway mucus, the formation of pathologic mucus, the failure of mucus clearance that results in symptoms and abnormal lung function and the therapy of mucus dysfunction.…”

Section: Lung Lung Cancermentioning

confidence: 99%

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

et al. 2015

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Mucins are major glycoprotein components of the mucus that coats the surfaces of cells lining the respiratory, digestive, gastrointestinal and urogenital tracts. They function to protect epithelial cells from infection, dehydration and physical or chemical injury, as well as to aid the passage of materials through a tract i.e., lubrication. They are also implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells. In Human there are two types of mucins, membrane-bound and secreted that are originated from mucous producing goblet cells localized in the epithelial cell layer or in mucous producing glands and encoded by MUC gene. Mucins belong to a heterogeneous family of high molecular weight proteins composed of a long peptidic chain with a large number of tandem repeats that form the so-called mucin domain. The molecular weight is generally high, ranging between 0.2 and 10 million Dalton and all mucins contain one or more domains which are highly glycosylated. The size and number of repeats vary between mucins and the genetic polymorphism represents number of repeats (VNTR polymorphisms), which means the size of individual mucins can differ substantially between individuals which can be used as markers. In human it is only MUC1 and MUC7 that have mucin domains with less than 40% serine and threonine which in turn could reduce number of PTS domains. Mucins can be considered as powerful two-edged sword, as its normal function protects from unwanted substances and organisms at an arm's length while, malfunction of mucus may be an important factor in human diseases. In this review we have unearthed the current status of different mucin proteins in understanding its role and function in various non-communicable diseases in human with special reference to its organ specific locations. The findings described in this review may be of direct relevance to the major research area in biomedicine with reference to mucin and mucin associated diseases.

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Mucin Overproduction in Chronic Inflammatory Lung Disease

Cited by 69 publications

References 141 publications

Absence of Proteinase-Activated Receptor-1 Signaling in Mice Confers Protection from fMLP-Induced Goblet Cell Metaplasia

Absence of Proteinase-Activated Receptor-1 Signaling in Mice Confers Protection from fMLP-Induced Goblet Cell Metaplasia

Нозоспецифічні Особливості Редокс-Процесів При Муковісцидозі

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

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