Injury Activates a Dynamic Cytoprotective Network to Confer Stress Resilience and Drive Repair
| العنوان: | Injury Activates a Dynamic Cytoprotective Network to Confer Stress Resilience and Drive Repair |
|---|---|
| المؤلفون: | Will Wood, Paul Martin, Helen Weavers |
| المصدر: | Weavers, H, Wood, W & Martin, P 2019, ' Injury Activates a Dynamic Cytoprotective Network to Confer Stress Resilience and Drive Repair ', Current Biology, vol. 29, no. 22, pp. 3851-3862.e4 . https://doi.org/10.1016/j.cub.2019.09.035 Weavers, H, Wood, W & Martin, P 2019, ' Injury activates a dynamic cytoprotective network to confer stress resilience and drive repair ', Current Biology, vol. 29, no. 22, pp. 3851-3862.e4 . https://doi.org/10.1016/j.cub.2019.09.035 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, DNA damage, MAP Kinase Signaling System, NF-E2-Related Factor 2, wound, Inflammation, tissue resilience, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, cytoprotection, hormesis, preconditioning, medicine, Animals, Drosophila Proteins, oxidative stress, tissue repair, chemistry.chemical_classification, Reactive oxygen species, Wound Healing, Gadd45, Mechanism (biology), Hormesis, Intracellular Signaling Peptides and Proteins, ROS, Cytoprotection, 3. Good health, Cell biology, Oxidative Stress, 030104 developmental biology, Drosophila melanogaster, chemistry, inflammation, Calcium, medicine.symptom, General Agricultural and Biological Sciences, Reactive Oxygen Species, Oxidation-Reduction, 030217 neurology & neurosurgery, Oxidative stress |
| الوصف: | In healthy individuals, injured tissues rapidly repair themselves following damage. Within a healing skin wound, recruited inflammatory cells release a multitude of bacteriocidal factors, including reactive oxygen species (ROS), to eliminate invading pathogens. Paradoxically, while these highly reactive ROS confer resistance to infection, they are also toxic to host tissues and may ultimately delay repair. Repairing tissues have therefore evolved powerful cytoprotective “resilience” machinery to protect against and tolerate this collateral damage. Here, we use in vivo time-lapse imaging and genetic manipulation in Drosophila to dissect the molecular and cellular mechanisms that drive tissue resilience to wound-induced stress. We identify a dynamic, cross-regulatory network of stress-activated cytoprotective pathways, linking calcium, JNK, Nrf2, and Gadd45, that act to both “shield” tissues from oxidative damage and promote efficient damage repair. Ectopic activation of these pathways confers stress protection to naive tissue, while their inhibition leads to marked delays in wound closure. Strikingly, the induction of cytoprotection is tightly linked to the pathways that initiate the inflammatory response, suggesting evolution of a fail-safe mechanism for tissue protection each time inflammation is triggered. A better understanding of these resilience mechanisms—their identities and precise spatiotemporal regulation—is of major clinical importance for development of therapeutic interventions for all pathologies linked to oxidative stress, including debilitating chronic non-healing wounds. |
| وصف الملف: | application/pdf; text/html |
| اللغة: | English |
| DOI: | 10.1016/j.cub.2019.09.035 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::948394da875f866de6565b5ff0d0be84 https://research-information.bris.ac.uk/en/publications/a7482ced-5b93-4ba5-a92a-5fecf8314214 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....948394da875f866de6565b5ff0d0be84 |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.1016/j.cub.2019.09.035 |
|---|