High density lipoprotein promotes proliferation of adipose-derived stem cells via S1P1 receptor and Akt, ERK1/2 signal pathways.
High density lipoprotein promotes proliferation of adipose-derived stem cells via S1P1 receptor and Akt, ERK1/2 signal pathways.
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高密度脂蛋白通过S1P1受体和Akt、ERK1/2信号通路促进脂肪干细胞增殖。
DOI：
10.1186/s13287-015-0090-5
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发表时间：
2015-05-15
影响因子：
7.5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Shen H;Zhou E;Wei X;Fu Z;Niu C;Li Y;Pan B;Mathew AV;Wang X;Pennathur S;Zheng L;Wang Y
脂肪源性干细胞（ADSC）是非造血间充质干细胞，在分化为多种细胞谱系的能力方面显示出巨大的前景。它们无处不在的性质和易于采集的特性吸引了许多研究人员的注意，它们成为再生医学应用的理想候选者。一些报告表明，移植 ADSC 可以促进动物模型中受损组织的修复和血管生成。移植后这些细胞的存活仍然是 ADSC 移植成功的关键限制因素。众所周知，高密度脂蛋白 (HDL) 等循环因子可通过增殖和抑制细胞凋亡来促进其他干细胞（如骨髓干细胞和内皮祖细胞）的存活。 HDL 对体内移植的脂肪干细胞的影响尚不清楚。本研究重点探讨血浆 HDL 对 ADSC 的影响，并阐明其进入血液后增殖的机制。使用 MTT 和 BrdU 测定，我们测试了 HDL 对 ADSC 增殖的影响。我们使用蛋白质印迹法探讨了 ADSC 中下游细胞内 Akt 和 ERK1/2 信号通路以及细胞周期蛋白的表达。我们的研究发现HDL通过与细胞膜上的1-磷酸鞘氨醇受体1（S1P1）结合来促进ADSC的增殖。这种相互作用导致细胞内Akt和ERK1/2信号通路的激活，导致细胞周期蛋白D1和细胞周期蛋白E的表达增加，同时细胞周期蛋白依赖性激酶抑制剂p21和p27的表达减少，从而促进细胞周期进展和细胞增殖。这些研究提出了 HDL 可能是干细胞生理调节剂的可能性，并且增加 HDL 浓度可能是促进 ADSC 移植的有价值的策略。本文的在线版本 (doi:10.1186/s13287-015-0090-5) 包含补充材料，可供授权用户使用。
Adipose-derived stem cells (ADSC) are non-hematopoietic mesenchymal stem cells that have shown great promise in their ability to differentiate into multiple cell lineages. Their ubiquitous nature and the ease of harvesting have attracted the attention of many researchers, and they pose as an ideal candidate for applications in regenerative medicine. Several reports have demonstrated that transplanting ADSC can promote repair of injured tissue and angiogenesis in animal models. Survival of these cells after transplant remains a key limiting factor for the success of ADSC transplantation. Circulating factors like High Density Lipoprotein (HDL) has been known to promote survival of other stems cells like bone marrow derived stem cells and endothelial progenitor cells, both by proliferation and by inhibiting cell apoptosis. The effect of HDL on transplanted adipose-derived stem cells in vivo is largely unknown. This study focused on exploring the effects of plasma HDL on ADSC and delineating the mechanisms involved in their proliferation after entering the bloodstream. Using the MTT and BrdU assays, we tested the effects of HDL on ADSC proliferation. We probed the downstream intracellular Akt and ERK1/2 signaling pathways and expression of cyclin proteins in ADSC using western blot. Our study found that HDL promotes proliferation of ADSC, by binding to sphingosine-1- phosphate receptor-1(S1P1) on the cell membrane. This interaction led to activation of intracellular Akt and ERK1/2 signaling pathways, resulting in increased expression of cyclin D1 and cyclin E, and simultaneous reduction in expression of cyclin-dependent kinase inhibitors p21 and p27, therefore promoting cell cycle progression and cell proliferation. These studies raise the possibility that HDL may be a physiologic regulator of stem cells and increasing HDL concentrations may be valuable strategy to promote ADSC transplantation. The online version of this article (doi:10.1186/s13287-015-0090-5) contains supplementary material, which is available to authorized users.
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影响因子：
5.5
作者：
He, Xiaoli;H'ng, Shiau-Chen;Melendez, Alirio J.
通讯作者：
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影响因子：
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DOI：
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DOI：
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发表时间：
2005-07-01
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