Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Sharan Janjuha - , Deutsche Forschungsgemeinschaft, Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Autor:in)
  • Sumeet Pal Singh - , Pancreatic beta-cell Biology and Regeneration (NFoG), Deutsche Forschungsgemeinschaft, DFG Ctr Regenerat Therapies Dresden Cluster Exc (Autor:in)
  • Anastasia Tsakmaki - , Queen Mary University of London (Autor:in)
  • S. Neda Mousavy Gharavy - , Imperial College London (Autor:in)
  • Priyanka Murawala - , Deutsche Forschungsgemeinschaft, DFG Ctr Regenerat Therapies Dresden Cluster Exc (Autor:in)
  • Judith Konantz - , Core Facility Fischhaltung, Deutsche Forschungsgemeinschaft, DFG Ctr Regenerat Therapies Dresden Cluster Exc (Autor:in)
  • Sarah Birke - , Deutsche Forschungsgemeinschaft (Autor:in)
  • David J. Hodson - , University of Birmingham (Autor:in)
  • Guy A. Rutter - , Imperial College London (Autor:in)
  • Gavin A. Bewick - , Queen Mary University of London (Autor:in)
  • Nikolay Ninov - , Deutsches Zentrum für Neurodegenerative Erkrankungen, Standort Dresden (Partner: DZNE der Helmholtzgemeinschaft), Professur für Zellbiologie und Regeneration von Betazellen, Deutsche Forschungsgemeinschaft, DFG Ctr Regenerat Therapies Dresden Cluster Exc, Universitätsklinikum AKH Wien, Technische Universität Dresden, German Center for Diabetes Research (Autor:in)

Abstract

The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is 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 tnf alpha-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 signaling(hi) 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.

Details

OriginalspracheEnglisch
Seitenumfang24
FachzeitschrifteLife
Jahrgang7
PublikationsstatusVeröffentlicht - 6 Apr. 2018
Peer-Review-StatusJa

Externe IDs

PubMed 29624168
Scopus 85046843174

Schlagworte

Schlagwörter

  • Endoplasmic-reticulum stress, Large gene lists, In-vivo, Life, Replication, Activation, Apoptosis, Survival, Pathway, Glucose