| Autor: |
Christina Wagner, Karin Uliczka, Judith Bossen, Xiao Niu, Christine Fink, Marcus Thiedmann, Mirjam Knop, Christina Vock, Ahmed Abdelsadik, Ulrich M. Zissler, Kerstin Isermann, Holger Garn, Mario Pieper, Michael Wegmann, Andreas R. Koczulla, Claus F. Vogelmeier, Carsten B. Schmidt-Weber, Heinz Fehrenbach, Peter König, Neil Silverman, Harald Renz, Petra Pfefferle, Holger Heine, Thomas Roeder |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 35, Iss 1, Pp 108956- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2021.108956 |
| Popis: |
Summary: Extensive remodeling of the airways is a major characteristic of chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). To elucidate the importance of a deregulated immune response in the airways for remodeling processes, we established a matching Drosophila model. Here, triggering the Imd (immune deficiency) pathway in tracheal cells induced organ-wide remodeling. This structural remodeling comprises disorganization of epithelial structures and comprehensive epithelial thickening. We show that these structural changes do not depend on the Imd pathway’s canonical branch terminating on nuclear factor κB (NF-κB) activation. Instead, activation of a different segment of the Imd pathway that branches off downstream of Tak1 and comprises activation of c-Jun N-terminal kinase (JNK) and forkhead transcription factor of the O subgroup (FoxO) signaling is necessary and sufficient to mediate the observed structural changes of the airways. Our findings imply that targeting JNK and FoxO signaling in the airways could be a promising strategy to interfere with disease-associated airway remodeling processes. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
