Epithelial basement membrane thickening is related to <scp>TGF</scp>‐Beta 1 expression in children with chronic respiratory diseases

Hoňková, Lenka; Uhlı́k, Jir̆ı́; Beránková, Katarína; Svobodová, Tamara; Pohunek, Petr

doi:10.1111/pai.12275

Cited by 16 publications

(11 citation statements)

References 30 publications

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“…Initial changes leading to remodeling, including thickness of the basement membrane (BM), subepithelial deposition of laminin, and collagen IV in the BM, have been defined as starting at less than 4 years of age in asymptomatic children predisposed to asthma . Similar structural changes in bronchial mucosa have been described in children with asthma, cystic fibrosis, and primary ciliary dyskinesia . This might suggest a common feature of bronchial remodeling in chronic respiratory diseases.…”

Section: Origins Of Asthma and Allergic Rhinitismentioning

confidence: 98%

Asthma and allergic rhinitis in childhood: what's new

Mastrorilli

Posa

Cipriani

et al. 2016

Pediatric Allergy Immunology

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Novel approaches are currently offered for the diagnostic workup and therapeutic management of allergic rhinitis and asthma. New predictive biomarkers of allergy and asthma are available. Primary and secondary prevention, earlier intervention, and modification of the natural history of allergic rhinitis and asthma are being intensively investigated. This review highlights advances in the understanding of the etiology, diagnosis, and management of atopic airway diseases in childhood, as well as prenatal and early-life risk factors and strategies for prevention.

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Section: Origins Of Asthma and Allergic Rhinitismentioning

confidence: 98%

Asthma and allergic rhinitis in childhood: what's new

Mastrorilli

Posa

Cipriani

et al. 2016

Pediatric Allergy Immunology

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“…Despite the existence of multiple clinical endotypes, most forms of asthma exhibit a dysregulated epithelial barrier. Asthmatic epithelium is characterized by an increase in basal and goblet cells 18 and a decrease in terminally differentiated ciliated cells, frequently accompanied by basement membrane thickening 19, 20 and epithelial shedding with the formation of Creola bodies consisting of clusters of shed epithelium (even in mild forms of disease) 21–23 . Disruption of epithelial tight and adherens junctions is typical for asthma, with marked loss of E-cadherin 24 and claudin-18 25 .…”

Section: Barrier Defects In Type 2 Diseasesmentioning

confidence: 99%

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

143

122

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Epithelial barriers of the skin, gastrointestinal tract and airway serve common critical functions such as maintaining a physical barrier against environmental insults and allergens, as well as providing a tissue interface balancing the communication between the internal and external environments. We now understand that in allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed towards loss of differentiation, reduced junctional integrity and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in the initiation of allergic disease, many important questions remain to be answered regarding the mechanisms disrupting the normal barrier function. Although our external environment (proteases, allergens, injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction, using both systems biology tools and causality-driven laboratory experimentation, will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergy.

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“…TGFis also expressed in eosinophils, one of the key in ammatory cells in asthma, and its expression therein is upregulated in severe asthma 20,21 . Recent reports also indicated that TGF-expression correlates with the thickening of the basement membrane in children with asthma, even though these patients were using inhaled corticosteroids 22 . In concordance with this and as we demonstrated in this study, TGF-might contribute to the pathogenesis of airway remodeling through the upregulation of endothelin-1 expression in the bronchial epithelium.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor-alpha and Transforming Growth Factor-beta Synergistically Upregulate Endothelin-1 Expression in Human Bronchial Epithelial Cells BEAS-2B

Tsuchiya

Wakabayashi

Matsukura

et al. 2016

Showa Univ J Med Sci

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: Endothelin-1 is a peptide with many functions including bronchoconstriction and the stimulation of fibroblasts, and myofibroblasts, and airway smooth muscle cell proliferation. These functions are related to airway remodeling and endothelin-1 is known to be upregulated in the epithelium of patients with severe asthma. We thus sought to elucidate the mechanisms underlying endothelin-1 expression in bronchial epithelial cells in vitro. The human bronchial epithelial cell line BEAS-2B was grown in culture and then treated with tumor necrosis factoralpha TNF-, interleukin-4 IL-4 , interleukin-13 IL-13 , and transforming growth factor-beta TGF-. Expression of endothelin-1 mRNA and protein was quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. We also repressed expression of the key transcription factor in the pathogenesis of severe asthma, nuclear factor-kappa B NF-B , using small interfering RNA siRNA . TNF-and TGF-signi cantly increased the release of endothelin-1 protein into the culture medium of BEAS-2B cells at 24 h after treatment compared to untreated cells ; however, the Th2 cytokines, IL-4 and IL-13, had no effect. Endothelin-1 mRNA expression was also upregulated by TNFand TGFwith a peak time point at 4 h after stimulation. Finally, the combination of TNF-and TGF-synergistically increased both endothelin-1 protein secretion and mRNA expression, and this upregulation was signi cantly suppressed in cells transfected with siRNA to repress NF-B expression. TNF-and TGF-synergistically upregulate the expression of endothelin-1 in human bronchial epithelial cells, possibly via the activity of NF-B. Our ndings thus suggest NFBa as a potential therapeutic target for the regulation of airway remodeling.

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Epithelial basement membrane thickening is related to TGF‐Beta 1 expression in children with chronic respiratory diseases

Cited by 16 publications

References 30 publications

Asthma and allergic rhinitis in childhood: what's new

Asthma and allergic rhinitis in childhood: what's new

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Tumor Necrosis Factor-alpha and Transforming Growth Factor-beta Synergistically Upregulate Endothelin-1 Expression in Human Bronchial Epithelial Cells BEAS-2B

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