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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00428

RNase A promotes proliferation of neuronal progenitor cells via an ERK-dependent pathway

 Hsin-Yu Liu1,  Chiung-Ya Chen1, Yun-Fen Hung1, Hong-Ru Lin1, Pu-Yun Shih1, Chi-Ning Chuang1, Wei-Ping Li1,  Tzyy-Nan Huang1 and  Yi-Ping Hsueh1*
  • 1Institute of Molecular Biology, Academia Sinica, Taiwan

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.

Keywords: Erk activation, Neural progenitor cell proliferation, RNase A, RNase 1, Neurogenesis

Received: 27 Aug 2018; Accepted: 05 Nov 2018.

Edited by:

Enrico Tongiorgi, University of Trieste, Italy

Reviewed by:

Daniele Bottai, Università degli Studi di Milano, Italy
Tara L. Walker, Queensland Brain Institute, University of Queensland, Australia  

Copyright: © 2018 Liu, Chen, Hung, Lin, Shih, Chuang, Li, Huang and Hsueh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yi-Ping Hsueh, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, yph@gate.sinica.edu.tw