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Kılıç, A.* ; Sonar, S.S.* ; Yildirim, A.Ö. ; Fehrenbach, H.* ; Nockher, W.A.* ; Renz, H.*

Nerve growth factor induces type III collagen production in chronic allergic airway inflammation.

J. Allergy Clin. Immunol. 128, 1058-1066 (2011)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Excessive extracellular matrix deposition occurs as a result of repetitive injury-repair cycles and plays a central role in the pathogenesis of chronic inflammatory diseases, such as allergic asthma. The molecular mechanism leading to aberrant collagen deposition is not fully understood. We sought to test the hypothesis that increased nerve growth factor (NGF) production contributes to collagen deposition in the airways during chronic allergic airway inflammation. Antibody-blocking experiments were performed in an in vivo model for chronic allergic airway inflammation (allergic asthma), which is accompanied by matrix deposition in the subepithelial compartment of the airways, to study the profibrotic effect of NGF. The signaling pathways were delineated with in vivo and in vitro studies in primary lung fibroblasts. Functional blocking of NGF in chronically affected mice markedly prevented subepithelial fibrosis. Transgenic overexpression of NGF in murine airways resulted in altered airway wall morphology with increased peribronchial collagen deposition and impaired lung physiology in the absence of inflammation. NGF exerted a direct effect on collagen expression in murine lung fibroblasts, which was mainly mediated through the activation of the receptor tropomyosin-related kinase A. NGF-induced collagen expression was dependent on downstream activation of p38 mitogen-activated protein kinase independent of the TGF-β1/mothers against decapentaplegic homolog (SMAD) pathway.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Allergic asthma; airway remodeling; type III collagen; nerve growth factor
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Quellenangaben Band: 128, Heft: 5, Seiten: 1058-1066 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)