Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells
Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells
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DOI：
10.4161/epi.22609
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发表时间：
2012-12-01
期刊：
影响因子：
3.7
通讯作者：
Cinar, Mehmet Ulas
中科院分区：
文献类型：
--
作者：
Fan, Huitao;Zhang, Rui;Cinar, Mehmet Ulas
卫星细胞作为骨骼肌干细胞，支持出生后肌肉的生长和损伤或疾病后的再生。通过靶向该细胞群中的肌生长抑制素（MSTs），对于改善家畜的肌肉性能和治疗人类的肌肉病理有很大的希望。人类饮食中含有许多组蛋白去乙酰化酶（HDAC）抑制剂，如萝卜硫素（SFN），其对卫星细胞中MMP 3基因的表观遗传学影响尚不清楚。因此，我们的目的是研究SFN对卫星细胞中MMP 3基因的表观遗传影响。目前的工作提供了第一个证据，这是不同的效果，阿司他丁A（TSA），SFN补充在体外不仅作为HDAC抑制剂，但也作为DNA甲基转移酶（DNMT）抑制剂在猪卫星细胞。与TSA和5-氮杂-2 '-脱氧胞苷（5-aza-dC）相比，SFN处理显著抑制MclO表达，伴随着MclO信号通路的负反馈抑制剂的强烈减弱的表达。靶向MRNA的miRNA不参与MRNA的转录后调节。然而，一个弱富集成肌细胞决定（MyoD）蛋白与减少组蛋白乙酰化在MyoD结合位点位于MclO启动子区域可能有助于MclO的转录抑制SFN。这些发现揭示了生物活性化合物SFN的表观遗传抑制MMPs的新模式。因此，SFN在卫星细胞中的这种新的药理学、生物学活性可以允许开发新的方法来削弱MMPs信号传导途径，用于人类骨骼肌疾病的治疗和牲畜生产的改善。
Satellite cells function as skeletal muscle stem cells to support postnatal muscle growth and regeneration following injury or disease. There is great promise for the improvement of muscle performance in livestock and for the therapy of muscle pathologies in humans by the targeting of myostatin (MSTN) in this cell population. Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown. Therefore, we aimed to investigate the epigenetic influences of SFN on the MSTN gene in satellite cells. The present work provides the first evidence, which is distinct from the effects of trichostatin A (TSA), that SFN supplementation in vitro not only acts as a HDAC inhibitor but also as a DNA methyltransferase (DNMT) inhibitor in porcine satellite cells. Compared with TSA and 5-aza-2'-deoxycytidine (5-aza-dC), SFN treatment significantly represses MSTN expression, accompanied by strongly attenuated expression of negative feedback inhibitors of the MSTN signaling pathway. miRNAs targeting MSTN are not implicated in posttranscriptional regulation of MSTN. Nevertheless, a weakly enriched myoblast determination (MyoD) protein associated with diminished histone acetylation in the MyoD binding site located in the MSTN promoter region may contribute to the transcriptional repression of MSTN by SFN. These findings reveal a new mode of epigenetic repression of MSTN by the bioactive compound SFN. This novel pharmacological, biological activity of SFN in satellite cells may thus allow for the development of novel approaches to weaken the MSTN signaling pathway, both for therapies of human skeletal muscle disorders and for livestock production improvement.