PUBLICATION
Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
- Authors
- 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.
- ID
- ZDB-PUB-180407-3
- Date
- 2018
- Source
- eLIFE 7: (Journal)
- Registered Authors
- Ninov, Nikolay, Singh, Sumeet Pal
- Keywords
- cell biology, zebrafish
- Datasets
- GEO:GSE106938
- MeSH Terms
-
- Inflammation Mediators/metabolism*
- Cell Proliferation*
- Gene Expression Profiling
- NF-kappa B/genetics
- NF-kappa B/metabolism*
- Signal Transduction
- Cells, Cultured
- Animals, Genetically Modified
- Insulin-Secreting Cells/immunology
- Insulin-Secreting Cells/metabolism
- Insulin-Secreting Cells/pathology*
- Transcriptional Activation
- Inflammation/immunology
- Inflammation/metabolism
- Inflammation/pathology*
- Animals
- Single-Cell Analysis
- Zebrafish/immunology
- Zebrafish/physiology*
- Aging*
- PubMed
- 29624168 Full text @ Elife
Citation
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. 7.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping