bta-miR-23a involves in adipogenesis of progenitor cells derived from fetal bovine skeletal muscle.
bta-miR-23a involves in adipogenesis of progenitor cells derived from fetal bovine skeletal muscle.
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bta-miR-23a 参与源自胎牛骨骼肌的祖细胞的脂肪形成
DOI：
10.1038/srep43716
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Guan L;Hu X;Liu L;Xing Y;Zhou Z;Liang X;Yang Q;Jin S;Bao J;Gao H;Du M;Li J;Zhang L
肌肉内脂肪沉积或大理石花纹是高质量牛肉的关键。骨骼肌成脂的分子机制在很大程度上仍不清楚。在本研究中，我们从胎牛骨骼肌中分离出血小板衍生生长因子受体α(PDGFRα)阳性的祖细胞，并将其诱导为脂肪细胞。通过miRNAome测序，我们发现BTA-miR-23a是一个在骨骼肌中介导牛脂肪形成的成脂miRNA。在PDGFRα+祖细胞分化过程中，bta-miR-23a的表达下调。强制表达BTa-miR-23a可模拟减少脂肪堆积，并抑制关键的成脂转录因子过氧化物酶体增殖性激活受体γ(PPARγ)和CCAAT/增强子结合蛋白α(C/EBPα)。而其抑制剂下调BTA-miR-23a则增加脂质积累，增加C/EBPα、PPARγ和脂肪酸结合蛋白4(FABP4)的表达。靶点预测分析表明，ZNF423是BTA-miR-23a的潜在靶点。双荧光素酶报告基因分析表明，BTA-miR-23a直接针对ZNF423的3‘-非编码区。总之，我们的数据表明，BTA-miR-23a作为一种抗成脂调节因子，通过靶向ZNF423来协调早期肌肉内成脂承诺。
Intramuscular fat deposition or marbling is essential for high quality beef. The molecular mechanism of adipogenesis in skeletal muscle remains largely unknown. In this study, we isolated Platelet-derived growth factor receptor α (PDGFRα) positive progenitor cells from fetal bovine skeletal muscle and induced into adipocytes. Using miRNAome sequencing, we revealed that bta-miR-23a was an adipogenic miRNA mediating bovine adipogenesis in skeletal muscle. The expression of bta-miR-23a was down-regulated during differentiation of PDGFRα+ progenitor cells. Forced expression of bta-miR-23a mimics reduced lipid accumulation and inhibited the key adipogenic transcription factor peroxisome proliferative activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα). Whereas down-regulation of bta-miR-23a by its inhibitors increased lipid accumulation and expression of C/EBPα, PPARγ and fatty acid-binding protein 4 (FABP4). Target prediction analysis revealed that ZNF423 was a potential target of bta-miR-23a. Dual-luciferase reporter assay revealed that bta-miR-23a directly targeted the 3′-UTR of ZNF423. Together, our data showed that bta-miR-23a orchestrates early intramuscular adipogeneic commitment as an anti-adipogenic regulator which acts by targeting ZNF423.