活性维生素D通过维生素D响应元件增加C2C12细胞中的肌原体分化,这种反应元件在肌原体促进物上存在
Kathryn H Alliband1, Tim Parr1, Preeti H Jethwa1
1Division of Food, Nutrition and Dietetics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.
Frontiers in physiology
|January 24, 2024
概括
活性维生素D (VD) 通过增加肌原蛋白转录来促进骨肌肉的发育,从而促进肌生成和更大的肌管. 这凸显了母体VD状态对胎儿肌肉发育的重要性.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 骨肌肉的发育涉及到肌细胞的增殖和分化.
- 维生素D (VD) 影响肌形成,但由于时间过程数据有限,其确切的作用尚不清楚.
- 孕产妇静脉疾病缺陷影响全球相当一部分孕妇,强调需要了解静脉疾病对胎儿肌肉发育的影响.
研究的目的:
- 阐明活性维生素D (1,25(OH) 2D3) 对C2C12肌体发生的时间依赖性影响.
- 为了研究1,25(OH) 2D3调节肌原蛋白表达的分子机制.
- 为了确定维生素D反应元 (VDRE) 在肌原蛋白促进体中的功能作用.
主要方法:
- 进行了8天的C2C12神经细胞分化时间课程,其度变化为1,25(OH) 2D3.3.
- 进行了DNA,肌酸激酶和蛋白质测定,以及用于肌原性基因表达的定量PCR (Myf5,MyoD,肌原蛋白,MHC异型).
- 使用野生类型和突变的肌原蛋白促进体的记者基因测定和染色体免疫沉 (ChIP) 来评估VDR与VDRE的结合.
主要成果:
- 1,25(OH) 2D3抑制了C2C12细胞的增殖和增强分化.
- 观察到Myf5,myogenin和所有测量的MHC异型 (新生儿,胚胎,IIa,IIx,IIb) 的表达增加与1,25(OH) 2D3治疗.
- 在肌原蛋白促进剂上对VDRE进行突变,取消了VD诱导的表达增加,ChIP证实VDR与VDRE结合.
结论:
- 活性维生素D通过在肌原蛋白促进体中的功能VDRE直接调高肌原蛋白转录.
- 这种机制导致增强的肌细胞分化,增加早期和晚期肌肉素重链 (MHC) 异型的表达,以及更大的肌肉管大小.
- 这些发现强调了怀孕期间VD状态对正常骨肌肉发育的关键作用,需要进一步的体内研究.
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