Liu Hsin-Yu, Chen Chiung-Ya, Hung Yun-Fen, Lin Hong-Ru, Chao Hsu-Wen, Shih Pu-Yun, Chuang Chi-Ning, Li Wei-Ping, Huang Tzyy-Nan, Hsueh Yi-Ping
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Front Mol Neurosci. 2018 Nov 26;11:428. doi: 10.3389/fnmol.2018.00428. eCollection 2018.
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 and . 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.
核糖核酸酶A（RNase A）超家族的成员调节各种生理过程。RNase A是RNase A超家族中研究最深入的成员，在包括大脑在内的不同组织中广泛表达。我们意外地发现，RNase A在体内和体外均可触发神经祖细胞（NPC）的增殖。RNase A处理可诱导解离的神经元培养物中的细胞增殖，并增加神经球培养物中的细胞量。BrdU（5-溴-2'-脱氧尿苷）标记证实了RNase A对细胞增殖的作用。那些分裂的细胞为巢蛋白和SOX2阳性，表明RNase A触发NPC增殖。增殖抑制剂阿糖胞苷完全抑制了RNase A对NPC数量的影响，进一步支持RNase A主要通过促进增殖来增加NPC数量。此外，我们发现RNase A处理增加了ERK磷酸化，而ERK途径的阻断抑制了RNase A对NPC增殖的作用。向小鼠脑室内注射RNase A可增加脑室下区5-乙炔基-2'-脱氧尿苷（EdU）或BrdU标记细胞的数量。那些由RNase A诱导的NPC能够迁移到其他脑区，包括海马体、杏仁核、皮质、纹状体和丘脑。总之，我们的研究表明，RNase A通过ERK依赖途径促进NPC增殖，并进一步丰富了RNase A家族的生理功能。
