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氧化型低密度脂蛋白通过抑制 Akt 磷酸化改变骨髓干细胞的行为并损害其内皮分化。

Ox-LDL modifies the behaviour of bone marrow stem cells and impairs their endothelial differentiation via inhibition of Akt phosphorylation.

机构信息

Davis Heart & Lung Research Institute and Division of Cardiovascular Medicine, Ohio State University Medical Center, Columbus, OH 43210, USA.

出版信息

J Cell Mol Med. 2011 Feb;15(2):423-32. doi: 10.1111/j.1582-4934.2009.00948.x.

DOI:10.1111/j.1582-4934.2009.00948.x
PMID:19863696
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3822806/
Abstract

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.

摘要

这项研究旨在探讨氧化型低密度脂蛋白（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（MAPCs）与 ox-LDL 孵育长达 2 周。ox-LDL 处理通过降低细胞增殖和增加细胞凋亡的组合，导致培养中的 MAPC 群体随时间和剂量依赖性减少。ox-LDL 以剂量和时间依赖的方式显著抑制 MAPC 中干细胞标志物 Oct-4 的表达。ox-LDL 显著抑制 MAPC 的内皮分化，内皮标志物 vWF、Flk-1 和 CD31 的表达明显减少，体外血管结构形成受损。ox-LDL 诱导的 MAPC 凋亡和 Oct-4 表达、细胞增殖和内皮分化的抑制与 Akt 磷酸化的显著抑制有关。用组成型激活 Akt 转染的 MAPC 中转染 Akt 过表达完全逆转了 ox-LDL 对 MAPC 的作用，包括增强的凋亡、减少的细胞增殖、抑制的 Oct-4 表达和内皮分化以及体外血管结构形成。总之，ox-LDL 通过抑制 Akt 信号通路促进 MAPC 的凋亡和抑制 Oct-4 表达和自我更新，并损害其内皮分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/34603501c361/jcmm0015-0423-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/1fb0f6d17610/jcmm0015-0423-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/b5349cdf06ce/jcmm0015-0423-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/f24796d8635b/jcmm0015-0423-f3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/7c0d453bc36e/jcmm0015-0423-f6a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/a19167f6348c/jcmm0015-0423-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/34603501c361/jcmm0015-0423-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/1fb0f6d17610/jcmm0015-0423-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/b5349cdf06ce/jcmm0015-0423-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/f24796d8635b/jcmm0015-0423-f3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/7c0d453bc36e/jcmm0015-0423-f6a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/a19167f6348c/jcmm0015-0423-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a41/3822806/34603501c361/jcmm0015-0423-f5.jpg

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