Suberoylanilide hydroxamic acid promotes cardiomyocyte differentiation of rat mesenchymal stem cells
Suberoylanilide hydroxamic acid promotes cardiomyocyte differentiation of rat mesenchymal stem cells
复制标题
辛二酰苯胺异羟肟酸促进大鼠间充质干细胞心肌细胞分化
DOI：
10.1016/j.yexcr.2009.05.005
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发表时间：
2009-10-15
影响因子：
3.7
通讯作者：
Tian, Jie
中科院分区：
文献类型：
--
作者：
Feng, Chuan;Zhu, Jing;Tian, Jie
研究辛二酰苯胺异羟肟酸（SAHA）对骨髓间充质干细胞（MSCs）心肌分化的影响。分离大鼠骨髓间充质干细胞，分别用SAHA、5-氮杂胞苷（5-aza，DNA甲基化抑制剂）或二者联合诱导分化为心肌细胞。SAHA处理7天后，心肌细胞特异性基因GATA 4、NKx 2.5和Mef 2c的转录表达在细胞中呈剂量依赖性增加，其mRNA水平比基线增加高达15倍。然而，这些基因的mRNA水平在5-氮杂处理的细胞中仅增加2-4倍。用SAHA诱导4周后，cTnT蛋白含量在细胞中以剂量依赖性方式大幅增加，最高达基线的8倍。相比之下，只有最小的cTnT蛋白被发现在5-氮杂处理的细胞。当用SAHA和5-aza处理MSC时，GATA 4、NKx 2.5和Mef 2c的mRNA水平和cTnT蛋白含量与单独用SAHA处理的细胞中的那些相同。上述结果表明，SAHA能有效地促进大鼠骨髓间充质干细胞在体外向心肌细胞分化。SAHA是比5-aza更有效的MSC心脏分化诱导剂。我们的数据还表明，SAHA和5-aza之间没有协同或拮抗作用的MSC的心肌细胞分化，组蛋白乙酰化，而不是DNA去甲基化，可能是决定大鼠MSC的心脏分化的主导机制。(C)2009年由Elsevier Inc.出版
This study was to investigate the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on cardiomyocyte differentiation of bone marrow mesenchymal stem cells (MSCs) in vitro. Rat MSCs were isolated and induced to differentiate into cardiomyocyte with SAHA or 5-azacytidine (5-aza, a DNA methylation inhibitor) or their combination. Following 7 days of SAHA treatment, the transcriptional expression of the cardiomyocyte-specific genes GATA4, NKx2.5, and Mef2c was dose-dependently increased in the cells with up to 15-fold increase in their mRNA levels over baseline. However, the mRNA levels of these genes were only increased by 2-4 fold in 5-aza-treated cells. After 4 weeks of induction with SAHA, cTnT protein content was substantially increased dose-dependently by up to 8-fold in the cells over the baseline. In contrast, only minimal cTnT protein was found in 5-aza-treated cells. When MSCs were treated with both SAHA and 5-aza, the mRNA levels of GATA4, NKx2.5, and Mef2c and cTnT protein content were the same as those in the cells treated with SAHA alone. These results indicate that SAHA effectively promotes cardiomyocyte differentiation of rat MSCs in vitro. SAHA was a much more potent inducer for cardiac differentiation of MSCs then 5-aza. Our data also indicate that no synergistic or antagonistic effect between SAHA and 5-aza on cardiomyocyte differentiation of MSCs is present, and histone acetylation, not DNA demethylation, may be the dominant mechanism that determines the cardiac differentiation of rat MSCs. (C) 2009 Published by Elsevier Inc.