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Titel:Nerve Growth Factor (NGF): ein pro-fibrotischer Faktor im Modell der chronisch allergischen Atemwegsentzündung
Autor:Kilic, Ayse
Weitere Beteiligte: Renz, Harald (Prof. Dr. med.)
Veröffentlicht:2010
URI:https://archiv.ub.uni-marburg.de/diss/z2011/0451
DOI: https://doi.org/10.17192/z2011.0451
URN: urn:nbn:de:hebis:04-z2011-04519
DDC: Medizin
Titel (trans.):Nerve Growth Factor (NGF): a pro-fibrotic factor in experimental chronic allergic airway inflammation
Publikationsdatum:2011-08-08
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
allergic asthma, Kollagen, Nervenwachstumsfaktor, Fibrose, nerve growth factor, collagen, airway remodeling, Allergisches Asthma

Zusammenfassung:
Die Gewebsfibrosierung, als ein Charakteristikum vieler chronisch entzündlicher Erkrankungen, wird mit der Beeinträchtigung der Organfunktion assoziiert. Sie wird als unvollständiger Reparaturversuch des Gewebes auf einen chronischen Entzündungsreiz verstanden. Beim allergischen Asthma manifestiert sich diese Fibrose im subepithelialen Bereich der Atemwege und trägt zur Verschlechterung der Lungenfunktion über die Progression der Erkrankung bei. Wachstumsfaktoren, die auf einen Entzündungsreiz hin von verletzten Epithel- und Entzündungszellen freigesetzt werden, dirigieren den sich anschließenden Reparaturversuch des Gewebes. Eine gesteigerte Expression dieser Faktoren im chronisch entzündeten Gewebe gilt als Ursache dieser Fibrosierung. Während der allergischen Atemwegsentzündung wird Nerve Growth Factor (NGF) sowohl vom Epithel als auch von Entzündungszellen in erhöhten Mengen produziert. Die dokumentierten wundheilungsfördernden Eigenschaften von NGF führten zu der Hypothese, dass NGF an der deregulierten Wundheilung beteiligt ist. Im Rahmen dieser Arbeit konnte erstmals die Rolle von NGF bei Fibrosierungsprozessen in der chronisch allergischen Atemwegsentzündung aufgezeigt werden. In Modellen der akuten und chronisch allergischen Atemwegsentzündung konnten, die strukturellen Veränderungen begleitend, erhöhte NGF-Konzentrationen nachgewiesen werden. Die Neutralisierung von NGF im Modell der chronisch allergischen Atemwegsentzündung der Maus blockierte die Bildung der subepithelialen Fibrose. In einem umgekehrten Ansatz konnten durch die selektive Überexpression von NGF in Atemwegsepithelien (NGF-Tg) strukturelle Veränderungen in den Atemwegen, die sich auf die Lungenphysiologie auswirkten, beobachtet werden. Die peribronchiale Fibrose in den Atemwegen NGF-Tg Mäuse bildete sich in Unabhängigkeit von einer lokalen Entzündung und unveränderten Transforming Growth Factor (TGF)β1-Konzentrationen aus. Sowohl in vivo- als auch in vitro- Experimente zeigten, dass NGF diesen Effekt über die Aktivierung des Rezeptors tropomyosin related kinase (Trk) A und nicht p75NTR vermittelte. Der identifizierte TGFβ1/mothers against decapentaplegic homolog (SMAD) unabhängige Signalweg über TrkA und p38 MAPK belegt die pro-fibrotische Aktivität von NGF. Damit konnte ein neuer Mechanismus zur Kollageninduktion, welcher auf der Aktivierung des NGF/TrkA Signalwegs beruht, identifiziert werden.

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