論文 - 詳細
| RRC ID | 64487 |
|---|---|
| 著者 | Wagner C, Uliczka K, Bossen J, Niu X, Fink C, Thiedmann M, Knop M, Vock C, Abdelsadik A, Zissler UM, Isermann K, Garn H, Pieper M, Wegmann M, Koczulla AR, Vogelmeier CF, Schmidt-Weber CB, Fehrenbach H, König P, Silverman N, Renz H, Pfefferle P, Heine H, Roeder T. |
| タイトル | Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways. |
| ジャーナル | Cell Rep |
| Abstract |
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. |
| 巻・号 | 35(1) |
| ページ | 108956 |
| 公開日 | 2021-4-6 |
| DOI | 10.1016/j.celrep.2021.108956 |
| PII | S2211-1247(21)00270-9 |
| PMID | 33826881 |
| MeSH | Airway Remodeling* Animals Drosophila Proteins / metabolism* Drosophila melanogaster / immunology* Epithelium / metabolism Epithelium / microbiology Forkhead Transcription Factors / metabolism* Hyperplasia Immunity* Life Cycle Stages MAP Kinase Kinase Kinases / metabolism Mitogen-Activated Protein Kinase Kinases / metabolism* Transcription Factors / metabolism |
| IF | 8.109 |
| リソース情報 | |
| ショウジョウバエ | DGRC#104412 |