Frontiers in Molecular Neuroscience (Nov 2018)

RNase A Promotes Proliferation of Neuronal Progenitor Cells via an ERK-Dependent Pathway

  • Hsin-Yu Liu,
  • Chiung-Ya Chen,
  • Yun-Fen Hung,
  • Hong-Ru Lin,
  • Hsu-Wen Chao,
  • Pu-Yun Shih,
  • Chi-Ning Chuang,
  • Wei-Ping Li,
  • Tzyy-Nan Huang,
  • Yi-Ping Hsueh

DOI
https://doi.org/10.3389/fnmol.2018.00428
Journal volume & issue
Vol. 11

Abstract

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Members of the ribonuclease A (RNase A) superfamily regulate various physiological processes. RNase A, the best-studied member of the RNase A superfamily, is widely expressed in different tissues, including brains. We unexpectedly found that RNase A can trigger proliferation of neuronal progenitor cells (NPC) both in vitro and in vivo. RNase A treatment induced cell proliferation in dissociated neuronal cultures and increased cell mass in neurosphere cultures. BrdU (5-Bromo-2'-Deoxyuridine) labeling confirmed the effect of RNase A on cell proliferation. Those dividing cells were Nestin- and SOX2-positive, suggesting that RNase A triggers NPC proliferation. The proliferation inhibitor Ara-C completely suppressed the effect of RNase A on NPC counts, further supporting that RNase A increases NPC number mainly by promoting proliferation. Moreover, we found that RNase A treatment increased ERK phosphorylation and blockade of the ERK pathway inhibited the effect of RNase A on NPC proliferation. Intracerebroventricular injection of RNase A into mouse brain increased the population of 5-ethynyl-2'-deoxyuridine (EdU) or BrdU-labeled cells in the subventricular zone. Those RNase A-induced NPCs were able to migrate into other brain areas, including hippocampus, amygdala, cortex, striatum, and thalamus. In conclusion, our study shows that RNase A promotes proliferation of NPCs via an ERK-dependent pathway and further diversifies the physiological functions of the RNase A family.

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