Total saponins of Panax ginseng (TSPG) promote erythroid differentiation of human CD34+ cells via EpoR-mediated JAK2/STAT5 signaling pathway
Total saponins of Panax ginseng (TSPG) promote erythroid differentiation of human CD34+ cells via EpoR-mediated JAK2/STAT5 signaling pathway
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DOI：
10.1016/j.jep.2009.08.043
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发表时间：
2009-11-12
影响因子：
5.4
通讯作者：
Wang, J.
中科院分区：
文献类型：
--
作者：
Chen, D.;Zuo, G.;Wang, J.
民族药理学相关性：从名贵中药人参中提取的主要成分人参总皂苷（TSPG）已被证明具有良好的造血作用。目的：探讨人参总皂苷促进人CD34(+)造血干细胞和祖细胞向红系分化的作用及其机制。 材料和方法：通过甲基纤维素测定系统和血红蛋白含量比色法测定TSPG对来自脐带血(UCB)的纯化CD34(+)细胞的红系分化的影响。分别采用Western blotting和流式细胞术检测脐带血单个核细胞（UCB-MNCs）和纯化的CD34（+）细胞中EpoR表达的变化，并在激光扫描共聚焦显微镜（LSCM）下观察。 RT-PCR检测CD34(+)细胞中EpoR mRNA的表达。采用免疫沉淀法分析TSPG预处理对Epo诱导的JAK(2)和STAT(5)酪氨酸磷酸化的影响。结果：添加TSPG(20-70 mg/L)提高了BFU-E的集落形成率。单独使用TSPG (50 mg/L)可显着增加血红蛋白含量，加入AG490可明显降低TSPG引起的血红蛋白含量升高。 TSPG增加CD34(+)细胞表面EpoR的表达，但不改变总UCB-MNCs中EpoR的表达。 TSPG还增加了CD34(+)细胞中EpoR mRNA的表达。 TSPG显着增强了UCB-MNCs中Epo诱导的JAK(2)和STAT(5)酪氨酸磷酸化。结论：这些结果表明TSPG可能通过Epo/EpoR介导的JAK(2)/STAT(5)信号通路增强造血干细胞和祖细胞的红系分化。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Ethnopharmacological relevance: Total saponins of Panax ginseng (TSPG), main constituents extracted from Panax ginseng, a highly valued traditional Chinese medicine, have been shown to be an effective agent on hematopoiesis.Objective: To investigate the effect and mechanism underlying in which TSPG promote human CD34(+) hematopoietic stem and progenitor cells to differentiate into erythroid-lineage cells.Materials and methods: The effect of TSPG on erythroid differentiation of purified CD34(+) cells derived from umbilical cord blood (UCB) was determined by methylcellulose assay system and colorimetry for hemoglobin content. The changes of EpoR expression in umbilical cord blood mononuclear cells (UCB-MNCs) and purified CD34(+) cells were detected with Western blotting and flow cytometry, respectively, and observed under laser scanning confocal microscope (LSCM). RT-PCR was performed to examine EpoR mRNA expression in CD34(+) cells. The effects of TSPG-pretreatment on Epo-induced JAK(2) and STAT(5) tyrosine phosphorylation were analyzed by immunoprecipitation.Results: The addition of TSPG (20-70 mg/L) increased the colony formation rate of BFU-E. TSPG (50 mg/L) alone used significantly increased the hemoglobin content, the addition of AG490 evidently reduced TSPG-induced elevation of hemoglobin content. TSPG increased the expression of EpoR on the surface membrane of CD34(+) cells but did not change the expression of EpoR in total UCB-MNCs. TSPG also increased the expression of EpoR mRNA in CD34(+) cells. TSPG markedly enhanced Epo-induced tyrosine phosphorylation of JAK(2) and STAT(5) in UCB-MNCs.Conclusion: These findings suggest that TSPG may enhance the erythroid differentiation of hematopoietic stem and progenitor cells via Epo/EpoR-mediated JAK(2)/STAT(5) signaling pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.