Acyclic retinoid induces differentiation and apoptosis of murine hepatic stem cells.
Acyclic retinoid induces differentiation and apoptosis of murine hepatic stem cells.
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DOI：
10.1186/s13287-015-0046-9
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发表时间：
2015-03-26
影响因子：
7.5
通讯作者：
Taniguchi H
中科院分区：
文献类型：
--
作者：
Guan HB;Nie YZ;Zheng YW;Takiguchi K;Yu HW;Zhang RR;Li B;Tsuchida T;Taniguchi H
无环类维生素A（ACR）是一种人工合成的维生素A，其治疗潜力已在实验和临床研究中得到证实。治疗靶点包括癌前和癌症干细胞。由于ACR也参与发育过程，因此应研究其对正常肝干细胞（HpSC）的影响以了解其潜在机制。在这里，我们研究了无环类视色素perretinoin对新鲜分离的小鼠HpSC的影响。我们使用流式细胞术从小鼠胎肝中分离c-kit− CD 29 + CD 49 f +/lowCD 45 − Ter 119 −细胞。为了评估ACR的效果，我们追踪克隆扩增，并通过免疫荧光染色和标记基因表达分析诱导过程中的细胞分化和凋亡。ACR剂量依赖性地抑制HpSC扩增。在培养过程中，干细胞克隆扩增明显受到抑制。此外，ACR显示出显着的促进HpSC分化和诱导细胞凋亡。干细胞标记基因Afp、Cd 44和Dlk的表达下调，而成熟肝细胞基因Alb和达特以及凋亡相关基因Annexin V和Caspase-3的表达上调。流式细胞仪检测结果显示，与对照组相比，ACR孵育后Annexin V阳性细胞的比例增加。通过白蛋白和Caspase-3免疫荧光染色获得的数据证实了基因表达的数据。最后，我们发现ACR直接调节视黄酸受体和维甲酸X受体的表达。这些结果表明，ACR抑制体外正常HpSCs的克隆扩增，并通过调节视黄酸受体促进未成熟细胞的分化。本文的在线版本（doi：10.1186/s13287-015-0046-9）包含补充材料，可供授权用户使用。
The therapeutic potential of acyclic retinoid (ACR), a synthetic retinoid, has been confirmed in experimental and clinical studies. Therapeutic targets include precancerous and cancer stem cells. As ACR is also involved in developmental processes, its effect on normal hepatic stem cells (HpSCs) should be investigated for understanding the underlying mechanisms. Here, we examined effects of the acyclic retinoid peretinoin on fresh isolated murine HpSCs. We isolated c-kit−CD29+CD49f+/lowCD45−Ter119− cells from murine fetal livers using flow cytometry. To evaluate the effect of ACR, we traced clonal expansion and analyzed cell differentiation as well as apoptosis during the induction process by immunofluorescent staining and marker gene expression. ACR dose-dependently inhibited HpSCs expansion. Stem cell clonal expansion was markedly inhibited during the culture period. Moreover, ACR showed a significant promotion of HpSC differentiation and induction of cellular apoptosis. The expression of stem cell marker genes, Afp, Cd44, and Dlk, was downregulated, while that of mature hepatocyte genes, Alb and Tat, and apoptosis-related genes, Annexin V and Caspase-3, were upregulated. Flow cytometry showed that the proportion of Annexin V-positive cells increased after ACR incubation compared with the control. Data obtained by immunofluorescent staining for albumin and Caspase-3 corroborated the data on gene expression. Finally, we found that ACR directly regulates the expression of retinoic acid receptors and retinoid X receptors. These findings indicate that ACR inhibits the clonal expansion of normal HpSCs in vitro and promotes the differentiation of immature cells by regulating receptors of retinoic acid. The online version of this article (doi:10.1186/s13287-015-0046-9) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
5.8
作者：
Liu HX;Ly I;Hu Y;Wan YJ
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Wan YJ
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作者：
DERSCH, H;ZILE, MH
通讯作者：
ZILE, MH
DOI：
10.1161/atvbaha.106.134114
发表时间：
2007-07-01
影响因子：
8.7
作者：
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通讯作者：
Nagai, Ryozo
影响因子：
13.5
作者：
Mishra, Lopa;Banker, Tanuj;Murray, Joseph;Byers, Stephen;Thenappan, Arun;He, Aiwu Ruth;Shetty, Kirti;Johnson, Lynt;Reddy, E. P.
通讯作者：
Reddy, E. P.