Joe I-Seul, Jeong Sin-Gu, Cho Goang-Won
Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, Republic of Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju 501-759, Republic of Korea.
Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, Republic of Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju 501-759, Republic of Korea.
Neurosci Lett. 2015 Jan 1;584:97-102. doi: 10.1016/j.neulet.2014.10.024. Epub 2014 Oct 22.
Resveratrol-3,4',5-trihydroxy-trans-stillbene (resveratrol; RSV), a natural non-flavonoid polyphenol compound, provides protection against stress injury, excessive sunlight, ultraviolet radiation, infections, and invading fungi. There is increasing evidence that resveratrol, a sirtuin1 activator, plays a pivotal role in neuroprotection and neuronal differentiation. In this study, we investigated whether resveratrol induces neuronal differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). Quantitative PCR results showed that resveratrol-treated MSCs (RSV-MSCs) had significantly increased expression of the neuroprogenitor markers Nestin, Musashi, CD133, and GFAP. When RSV-MSCs were differentiated with neuronal induction media (RSV-dMSCs), they exhibited a cell body and dendritic morphology similar to neurons. The number and neurite length of these RSV-dMSCs were significantly increased compared to differentiated MSCs (dMSCs). The RSV-dMSCs and dMSCs had significantly increased expression of the neuronal-specific marker genes Nestin, Musashi, CD133, GFAP, NF-M, MAP-2, and KCNH1. The RSV-dMSCs also showed a higher expression of the neuronal marker proteins, Nestin and NF-M, based on immunocytochemical staining and immunoblot analysis. This effect was abolished by the treatment of sirtuin1 inhibitor EX527. Therefore, we have shown that resveratrol treatment, along with the use of neuronal induction media, effectively stimulates neuronal cell differentiation of hBM-MSCs.
白藜芦醇-3,4',5-三羟基反式芪（白藜芦醇；RSV）是一种天然的非黄酮类多酚化合物，可抵御应激损伤、过度阳光照射、紫外线辐射、感染和入侵真菌。越来越多的证据表明，作为一种沉默调节蛋白1激活剂的白藜芦醇在神经保护和神经元分化中起关键作用。在本研究中，我们调查了白藜芦醇是否能诱导人骨髓间充质干细胞（hBM-MSCs）的神经元分化。定量PCR结果显示，经白藜芦醇处理的间充质干细胞（RSV-MSCs）中神经祖细胞标志物巢蛋白、神经干细胞标志物Musashi、CD133和胶质纤维酸性蛋白（GFAP）的表达显著增加。当RSV-MSCs用神经元诱导培养基进行分化时（RSV-dMSCs），它们呈现出与神经元相似的细胞体和树突形态。与分化的间充质干细胞（dMSCs）相比，这些RSV-dMSCs的数量和神经突长度显著增加。RSV-dMSCs和dMSCs中神经元特异性标志物基因巢蛋白、Musashi、CD133、GFAP、神经丝蛋白M（NF-M）、微管相关蛋白2（MAP-2）和钾通道亚家族H成员1（KCNH1）的表达显著增加。基于免疫细胞化学染色和免疫印迹分析，RSV-dMSCs还显示出更高的神经元标志物蛋白巢蛋白和NF-M的表达。用沉默调节蛋白1抑制剂EX527处理可消除这种作用。因此，我们已经表明，白藜芦醇处理以及使用神经元诱导培养基能有效刺激hBM-MSCs的神经元细胞分化。
