Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
| Autor: | Guy A. Rutter, Priyanka Murawala, Judith Konantz, Sarah Birke, Nikolay Ninov, Sumeet Pal Singh, S Neda Mousavy Gharavy, Sharan Janjuha, Gavin A. Bewick, Anastasia Tsakmaki, David J. Hodson |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Life Sciences & Biomedicine - Other Topics Aging GLUCOSE Animals Genetically Modified ACTIVATION PATHWAY 0302 clinical medicine ENDOPLASMIC-RETICULUM STRESS Insulin-Secreting Cells Gene expression cell biology NF-kB pancreas Biology (General) Zebrafish SOCS2 Cells Cultured IN-VIVO geography.geographical_feature_category General Neuroscience Diabetes NF-kappa B General Medicine Sciences bio-médicales et agricoles Islet APOPTOSIS medicine.anatomical_structure SURVIVAL beta-cells Medicine medicine.symptom Inflammation Mediators Single-Cell Analysis Pancreas Life Sciences & Biomedicine Signal Transduction Research Article Transcriptional Activation LARGE GENE LISTS QH301-705.5 Transgene Science Inflammation Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Downregulation and upregulation medicine Animals Cell Biology Cell Proliferation geography Science & Technology General Immunology and Microbiology Gene Expression Profiling biology.organism_classification zebrafish LIFE 030104 developmental biology REPLICATION Cancer research 030217 neurology & neurosurgery |
| Zdroj: | eLife 7:e32965 (2018) eLife, Vol 7 (2018) eLife, 7 eLife Janjuha, S, Singh, S P, Tsakmaki, A, Mousavy-Gharavy, N, Murawala, P, Konantz, J, Birke, S, Hodson, D J, Rutter, G, Bewick, G & Ninov, N N 2018, ' Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish ', eLife, vol. 7, e32965 . https://doi.org/10.7554/eLife.32965 |
| DOI: | 10.7554/eLife.32965 |
| Popis: | The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα-expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity. We link this heterogeneity to differences in gene expression and proliferation. Beta-cells with high NF-kB signaling proliferate significantly less compared to their neighbors with low activity. The NF-kB signalinghi cells also exhibit premature upregulation of socs2, an age-related gene that inhibits beta-cell proliferation. Together, our results show that NF-kB activity marks the asynchronous decline in beta-cell proliferation with advancing age. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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