TWEAK regulates proliferation and differentiation of adult neural progenitor cells.
The cytokine TWEAK is expressed in the brain and is induced in cerebral ischemia and other brain disorders. TWEAK regulates proliferation and differentiation of progenitor cells but its effect on adult neural progenitor cells is still unknown. Therefore, we investigated the proliferation of neural progenitor cells from the subventricular zone of adult mice in response to TWEAK treatment. TWEAK inhibited proliferation of neural progenitor cells through its membrane receptor Fn14. The reduced proliferation was not due to cell death. By using a reporter assay we found that TWEAK activated the transcription factor NF-κB in adult neural progenitor cells. Blockade of NF-κB signaling reversed the inhibition of cell proliferation by TWEAK. In addition, TWEAK induced neuronal differentiation of neural progenitor cells and lowered the expression of hes1, a transcription factor that prevents neuronal differentiation. In adult mice deficient of the TWEAK receptor Fn14, neurogenesis was reduced in the subventricular zone. In conclusion, our data show that TWEAK regulates adult neurogenesis in the subventricular zone by binding to the membrane receptor Fn14 and activating NF-κB.
Department of Pharmacology, University of Heidelberg, Germany.
Marion N
MN
Schölzke
Amely
A
Röttinger
Sasidhar
S
Murikinati
Nadine
N
Gehrig
Christoph
C
Leib
Markus
M
Schwaninger
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D000074049:Cytokine TWEAK; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*
D000074049:Cytokine TWEAK; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors