Sry-type HMG box 18 contributes to the differentiation of bone marrow-derived mesenchymal stem cells to endothelial cells.
Sry-type HMG box 18 contributes to the differentiation of bone marrow-derived mesenchymal stem cells to endothelial cells.
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DOI：
10.1016/j.diff.2015.03.003
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Agrawal DK
中科院分区：
文献类型：
--
作者：
Ikhapoh IA;Pelham CJ;Agrawal DK
在缺血性心脏病动物模型中，间充质干细胞（MSC）已显示出移植、分化或支持血管内皮细胞（EC）、平滑肌细胞和心肌细胞分化的治疗潜力。然而，在冠状动脉内或经心内膜输送间充质干细胞后，只有一小部分细胞移植，其中大多数细胞以未成熟细胞表型持续存在。本研究的目的是破译控制间充质干细胞分化为内皮细胞的分子途径和机制。已知血管内皮生长因子（VEGF-165）治疗可增强MSCs向内皮细胞的体外分化。我们测试了sry型HMG box （Sox）家族转录因子在这一过程中的可能参与。从尤卡坦微型猪的骨髓中分离MSCs，并进行10天的分化方案。Western blot或流式细胞术检测，VEGF-165 （50 ng/ml）体外处理MSCs诱导VEGFR-2、Sox9和Sox18蛋白表达显著增加，EC标记物PECAM-1、VE-cadherin和vWF的表达也显著增加。在MSCs中，sirna介导的Sox18（与Sox9相反）敲低可阻止vegf -165介导的EC标记物诱导和毛细血管形成。抑制VEGFR-2信号通路（SC-202850）可降低Sox18和vegf -165诱导的间充质干细胞向内皮细胞的分化。在这里，我们证明了VEGF-165通过vegfr -2依赖性诱导Sox18介导MSC向EC的分化，最终协调EC表型特定标记物的转录上调。
Mesenchymal stem cells (MSC) have shown therapeutic potential to engraft and either differentiate into or support differentiation of vascular endothelial cells (EC), smooth muscle cells and cardiomyocytes in animal models of ischemic heart disease. Following intracoronary or transendocardial delivery of MSCs, however, only a small fraction of cells engraft and the majority of those persist as an immature cell phenotype. The goal of the current study was to decipher the molecular pathways and mechanisms that control MSC differentiation into ECs. Vascular endothelial growth factor (VEGF-165) treatment is known to enhance in vitro differentiation of MSCs into ECs. We tested the possible involvement of the Sry-type HMG box (Sox) family of transcription factors in this process. MSCs were isolated from the bone marrow of Yucatan microswine and underwent a 10 day differentiation protocol. VEGF-165 (50 ng/ml) treatment of MSCs in vitro induced a significant increase in the protein expression of VEGFR-2, Sox9 and Sox18, in addition to the EC markers PECAM-1, VE-cadherin and vWF, as determined by Western blot or flow cytometry. siRNA-mediated knockdown of Sox18, as opposed to Sox9, in MSCs prevented VEGF-165-mediated induction of EC markers and capillary tube formation. Inhibition of VEGFR-2 signaling (SC-202850) reduced Sox18 and reduced VEGF-165-induced differentiation of MSCs to ECs. Here we demonstrate that VEGF-165 mediates MSC differentiation into ECs via VEGFR-2-dependent induction of Sox18, which ultimately coordinates the transcriptional upregulation of specific markers of the EC phenotype.
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影响因子：
4.1
作者：
Jager M;Quéinnec E;Le Guyader H;Manuel M
通讯作者：
Manuel M
影响因子：
3.1
作者：
Cai, J;Jiang, WG;Boulton, M
通讯作者：
Boulton, M
DOI：
10.1007/978-1-60761-705-1_5
发表时间：
2010-01-01
期刊：
STEM CELLS FOR MYOCARDIAL REGENERATION: METHODS AND PROTOCOLS
影响因子：
--
作者：
Boyle, Andrew J.;McNiece, Ian K.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
3.4
作者：
Forte, Amalia;Rinaldi, Barbara;Cipollaro, Marilena
通讯作者：
Cipollaro, Marilena
影响因子：
64.8
作者：
Francois, Mathias;Caprini, Andrea;Koopman, Peter
通讯作者：
Koopman, Peter