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

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Abstract

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.

Original languageEnglish
Article number428
JournalFrontiers in Molecular Neuroscience
Volume11
DOIs
Publication statusPublished - Nov 26 2018
Externally publishedYes

Keywords

  • ERK activation
  • Neural progenitor cells
  • Neurogenesis
  • Proliferation
  • RNase A

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Liu, H. Y., Chen, C. Y., Hung, Y. F., Lin, H. R., Chao, H. W., Shih, P. Y., Chuang, C. N., Li, W. P., Huang, T. N., & Hsueh, Y. P. (2018). Rnase a promotes proliferation of neuronal progenitor cells via an ERK-dependent pathway. Frontiers in Molecular Neuroscience, 11, [428]. https://doi.org/10.3389/fnmol.2018.00428