Shi Wentao, Bi Shiqi, Dai Yao, Yang Kaiyuan, Zhao Youfa, Zhang Zhijian
Department of Orthopedics, Gaochun People's Hospital, Nanjing, Jiangsu 211300, P.R. China.
Department of Embryology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1258-1266. doi: 10.3892/etm.2019.7692. Epub 2019 Jun 19.
Clobetasol propionate (Clo) is a potent topical glucocorticoid and a potential remyelinating agent that has been approved by the U.S. Food and Drug Administration. However, the effect of Clo on neural stem cells (NSCs) remains largely unknown. The aim of the present study was to investigate the effect of Clo on the differentiation of NSCs . NSCs were isolated from mouse embryonic brain tissues and expanded . The effect of Clo on NSC viability was examined using an MTT assay. Differentiating NSCs were treated with 5 or 10 µM Clo, or with DMSO control, and the degree of differentiation was examined following culture in stem cell differentiation induction medium for 7 days. The effect of Clo on NSC differentiation was assessed using immunocytochemistry and western blot analyses. The results revealed that Clo significantly increased NSC viability compared with the DMSO control group. Treatment with Clo also significantly increased the number of NSCs that differentiated into growth associated protein 43 positive neurons and corresponding axon lengths were also significantly increased. In addition, treatment with Clo significantly increased the number of myelin basic protein positive oligodendrocytes and decreased the number of glial fibrillary acidic protein positive astrocytes. Furthermore, inhibition of the sonic hedgehog and AMP-activated protein kinase signaling pathways inhibited Clo-induced NSC differentiation, and treatment with Clo upregulated the expression of several neurotrophic factors. In conclusion, the results of the current study suggest that Clo may have a potential therapeutic benefit in neurological disorders affecting oligodendrocytes and neurons.
丙酸氯倍他索（Clo）是一种强效局部糖皮质激素，也是一种潜在的髓鞘再生剂，已获美国食品药品监督管理局批准。然而，Clo对神经干细胞（NSCs）的影响在很大程度上仍不清楚。本研究的目的是探讨Clo对NSCs分化的影响。从小鼠胚胎脑组织中分离出NSCs并进行扩增。使用MTT法检测Clo对NSC活力的影响。将分化中的NSCs用5或10 μM Clo或二甲基亚砜（DMSO）对照处理，在干细胞分化诱导培养基中培养7天后检测分化程度。使用免疫细胞化学和蛋白质印迹分析评估Clo对NSC分化的影响。结果显示，与DMSO对照组相比，Clo显著提高了NSC活力。用Clo处理还显著增加了分化为生长相关蛋白43阳性神经元的NSCs数量，且相应的轴突长度也显著增加。此外，用Clo处理显著增加了髓鞘碱性蛋白阳性少突胶质细胞的数量，并减少了胶质纤维酸性蛋白阳性星形胶质细胞的数量。此外，抑制音猬因子和AMP激活的蛋白激酶信号通路可抑制Clo诱导的NSC分化，且用Clo处理可上调几种神经营养因子的表达。总之，本研究结果表明，Clo可能对影响少突胶质细胞和神经元的神经系统疾病具有潜在的治疗益处。
