Wang Li, Yu Li, Zhang Tianliang, Wang Lina, Leng Zhaoting, Guan Yingjun, Wang Xin
Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong, People's Republic of China.
Biotechnol Lett. 2014 Aug;36(8):1631-9. doi: 10.1007/s10529-014-1525-2. Epub 2014 Apr 19.
Neural stem cells (NSCs) are involved in neural tube formation. As the high-mobility group box 1 (HMGB1) protein is involved in neurulation and is present at elevated levels in neural tube defects (NTDs) induced by hyperthermia, we have now investigated the effects of HMGB1 on proliferation, differentiation, and MAPK signaling pathways of NSCs in vitro. We constructed a lentivirus vector with HMGB1 siRNA and used it to infect NSCs. Down-regulation of HMGB1 expression was confirmed. Proliferation of NSCs was determined by MTS and nestin/BrdU double-labeling. Differentiation of NSCs was assessed using β-tubulinIII and GFAP. Knockdown of HMGB1 significantly suppressed NSC proliferation but hardly affected differentiation, which was regulated by decreased expression of MAPK signaling pathways. Thus, HMGB1 has beneficial effects on neurulation and may serve as a new target for the prevention of NTDs.
神经干细胞（NSCs）参与神经管形成。由于高迁移率族蛋白B1（HMGB1）蛋白参与神经胚形成，且在热诱导的神经管缺陷（NTDs）中水平升高，我们现在研究了HMGB1对体外神经干细胞增殖、分化和MAPK信号通路的影响。我们构建了携带HMGB1 siRNA的慢病毒载体并用其感染神经干细胞。证实了HMGB1表达下调。通过MTS和巢蛋白/溴脱氧尿苷双标记法测定神经干细胞的增殖。使用β-微管蛋白III和胶质纤维酸性蛋白评估神经干细胞的分化。敲低HMGB1可显著抑制神经干细胞增殖，但几乎不影响分化，分化受MAPK信号通路表达降低的调节。因此，HMGB1对神经胚形成具有有益作用，可能成为预防神经管缺陷的新靶点。
