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RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury.

  • Zhu X University Children's Hospital Basel (UKBB), University of Basel, Basel, 4056, Switzerland. xinzhou.zhu@unibas.ch.
  • Yan J University Children's Hospital Basel (UKBB), University of Basel, Basel, 4056, Switzerland.
  • Bregere C Department of Biomedicine, University of Basel, Basel, 4056, Switzerland.
  • Zelmer A University Children's Hospital Basel (UKBB), University of Basel, Basel, 4056, Switzerland.
  • Goerne T University Children's Hospital Basel (UKBB), University of Basel, Basel, 4056, Switzerland.
  • Kapfhammer JP Department of Biomedicine, University of Basel, Basel, 4056, Switzerland.
  • Guzman R Department of Biomedicine, University of Basel, Basel, 4056, Switzerland.
  • Wellmann S University Children's Hospital Basel (UKBB), University of Basel, Basel, 4056, Switzerland. sven.wellmann@ukbb.ch.
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  • 2019-09-06
Published in:
  • Nature communications. - 2019
Animals
Animals, Newborn
Brain Injuries
Cells, Cultured
HEK293 Cells
Hippocampus
Humans
Hypoxia-Ischemia, Brain
Insulin-Like Growth Factor II
Lateral Ventricles
Male
Mice, Inbred C57BL
Mice, Knockout
Neural Stem Cells
Neurogenesis
RNA-Binding Proteins
Signal Transduction
Stem Cell Niche
English Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/92702
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