Inhibition of hepatic stellate cell proliferation by bone marrow mesenchymal stem cells via regulation of the cell cycle in rat.
Inhibition of hepatic stellate cell proliferation by bone marrow mesenchymal stem cells via regulation of the cell cycle in rat.
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DOI：
10.3892/etm.2012.628
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发表时间：
2012-09
影响因子：
2.7
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Qin S;Jiang H;Su S;Wang D;Liang Z;Zhang J;Yang W
本研究旨在观察大鼠骨髓间充质干细胞（MSCs）体外培养对肝星状细胞（HSC）RhoA信号转导因子及细胞周期调控因子P27和cyclin D1表达的影响。将大鼠HSC-T6和成纤维细胞分为对照组、阴性对照组和MSC实验组。使用WST 8测定法检查细胞增殖率。流式细胞仪分析细胞周期。采用RT-PCR和Western blot方法检测HSCs中细胞周期蛋白D1（cyclin D1）、RhoA和P27 mRNA和蛋白的表达。共培养12 h后，HSC可阻断MSCs从G 0/G1期向S期的转变。MSC实验组中RhoA mRNA和RhoA蛋白表达随时间呈下降趋势，与对照组和阴性对照组比较差异有统计学意义。MSC P27蛋白表达随时间延长呈上升趋势。RhoA与P27表达呈显著负相关。共培养24 h后，MSCs抑制cyclin D1的表达。实验组与对照组及阴性对照组比较，差异均有统计学意义（P<0.01）。总之，HSC与MSC的共培养能够抑制HSC增殖，促进凋亡并抑制RhoA表达。RhoA活性降低可诱导HSC中P27蛋白表达上调，从而促进MSC对cyclin D1的抑制，并诱导细胞周期停滞在G 0/G1期，表明其在抑制大鼠HSC增殖中的作用。
The present study aimed to observe the effect of rat bone marrow mesenchymal stem cells (MSCs) in vitro on hepatic stellate cell (HSC) RhoA signaling factors and the expression of the cell cycle regulators P27 and cyclin D1. Rat HSC-T6 and fibroblast cells were divided into control, negative control and MSC experimental groups. The cell proliferation rate was examined using the WST8 assay. The cell cycle was analyzed using flow cytometry. RT-PCR and western blot analysis were used to examine cyclin in D1 (cyclin D1), RhoA and P27 mRNA and protein expression in HSCs. After 12 h of co-culture, transition of the MSCs from the G0/G1 to S phase was blocked by HSCs. In the MSC experimental group, the RhoA mRNA and RhoA protein expression showed a decreasing trend with time, which was statistically significant compared with that in the control and negative control groups. MSC P27 protein expression showed an increasing trend with time. RhoA and P27 expression were significantly negatively correlated. After 24 h of co-culture, MSCs inhibited cyclin D1 expression. The difference was statistically significant in the experimental and control groups as well as in the negative control group (P<0.01). In conclusion, co-culture of HSCs with MSCs is capable of inhibiting HSC proliferation, promoting apoptosis and inhibiting RhoA expression. Reduced RhoA activity may induce an upregulation in P27 protein expression in HSCs, which promotes the inhibition of cyclin D1 by MSCs and induces cell cycle arrest at the G0/G1 phase, indicating a role in inhibiting rat HSC proliferation.
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影响因子：
3.1
作者：
Shi, Lijun;Li, Guozhong;Li, Hulun
通讯作者：
Li, Hulun
影响因子：
4.3
作者：
Anderson, Page A. W.;Muller-Borer, Barbara J.;Malouf, Nadia N.
通讯作者：
Malouf, Nadia N.
影响因子：
4.8
作者：
Weber, JD;Hu, WM;Baldassare, JJ
通讯作者：
Baldassare, JJ
影响因子：
2.6
作者：
Yannaki, E;Athanasiou, E;Fassas, A
通讯作者：
Fassas, A
影响因子：
64.5
作者：
TOYOSHIMA, H;HUNTER, T
通讯作者：
HUNTER, T