Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation.
Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation.
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DOI：
10.1111/j.1582-4934.2009.00948.x
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发表时间：
2011-02
影响因子：
5.3
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Chu L;Hao H;Luo M;Huang Y;Chen Z;Lu T;Zhao X;Verfaillie CM;Zweier JL;Liu Z
本研究旨在探讨氧化低密度脂蛋白（ox-LDL）对骨髓干细胞行为及其内皮分化的影响及其潜在机制。将成年大鼠骨髓多能祖细胞 (MAPC) 与 ox-LDL 一起孵育长达 2 周。 Ox-LDL 治疗通过细胞增殖减少和细胞凋亡增加的组合，导致培养物中 MAPC 群体呈时间和剂量依赖性减少。 ox-LDL 以剂量和时间依赖性方式显着抑制 MAPC 中干细胞标志物 Oct-4 的表达。 ox-LDL 显着抑制 MAPC 的内皮分化，显着降低内皮标志物 vWF、Flk-1 和 CD31 的表达，并损害体外血管结构的形成。 Ox-LDL 诱导的细胞凋亡以及对 Oct-4 表达、细胞增殖和 MAPC 内皮分化的抑制与 Akt 磷酸化的显着抑制相关。在用组成型活性 Akt 转染的 MAPC 中 Akt 过表达完全逆转了 ox-LDL 对 MAPC 的影响，包括增强细胞凋亡、减少细胞增殖、抑制 Oct-4 表达和内皮分化以及体外血管结构形成。总之，ox-LDL 促进细胞凋亡，抑制 Oct-4 表达和 MAPC 的自我更新，并通过抑制 Akt 信号传导损害其内皮分化。
This study was to investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the behaviour of bone marrow stem cells and their endothelial differentiation as well as the underlying mechanisms. Adult rat bone marrow multipotent progenitor cells (MAPCs) were incubated with ox-LDL for up to 2 weeks. Ox-LDL treatment resulted in a time- and dose-dependent reduction of MAPC population in culture through a combination of decreased cell proliferation and increased apoptosis. The expression of stem cell marker Oct-4 was significantly suppressed in MAPCs by ox-LDL in a dose- and time-dependant manner. Endothelial differentiation of MAPCs was substantially inhibited by ox-LDL with markedly decreased expression of endothelial markers vWF, Flk-1 and CD31, as well as impaired in vitro vascular structure formation. Ox-LDL-induced apoptosis and inhibition of Oct-4 expression, cell proliferation and endothelial differentiation of MAPCs were associated with significant inhibition of Akt phosphorylation. Akt overexpression in MAPCs transfected with a constitutively active Akt completely reversed the effects of ox-LDL on MAPCs including enhanced apoptosis, decreased cell proliferation, suppressed Oct-4 expression and endothelial differentiation as well as in vitro vascular structure formation. In conclusion, ox-LDL promotes apoptosis and inhibits Oct-4 expression and self-renewal of MAPCs, and impairs their endothelial differentiation via suppression of Akt signalling.
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DOI：
10.1016/j.bbrc.2005.12.211
发表时间：
2006-03-10
影响因子：
3.1
作者：
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