All-trans retinoic acid regulates sheep primary myoblast proliferation and differentiation in vitro
All-trans retinoic acid regulates sheep primary myoblast proliferation and differentiation in vitro
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DOI：
10.1016/j.domaniend.2019.106394
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发表时间：
2020-04-01
影响因子：
2.1
通讯作者：
Zhao, J.
中科院分区：
文献类型：
--
作者：
Li, Q.;Zhang, T.;Zhao, J.
维生素A及其代谢产物维甲酸（RA）在细胞分化和器官形态发生中起着关键作用。本研究旨在探讨维甲酸对绵羊原代成肌细胞增殖和分化的影响。分离绵羊原代成肌细胞，并用全反式维甲酸（ATRA，10 nM和100 nM）和溶剂处理。结果表明，10 nM ATRA可明显抑制细胞增殖，其作用机制可能是通过下调细胞周期蛋白D1（P < 0.05）、细胞周期蛋白依赖性激酶4（P < 0.05）和增殖细胞核抗原蛋白（P < 0.05）的丰度。与对照组相比，10 nM和100 nM ATRA均能促进肌管形成，增加肌细胞融合指数（P < 0.05），并与肌细胞生成素mRNA含量增加有关（P < 0.05）。ATRA能显著提高肌细胞生成素和肌球蛋白重链的表达水平（P < 0.01和P < 0.05）。有趣的是，ATRA处理增加了H3 K4 me 3在myogenin启动子区的富集，降低了H3 K27 me 3在myogenin启动子区的富集（P < 0.05）。100 nM ATRA可促进2-（N-（7-硝基苯-2-氧杂-1，3-二氮唑-4-基）氨基）-2-脱氧葡萄糖摄取（P < 0.05），并上调葡萄糖转运蛋白4的mRNA和蛋白表达（P < 0.05）。ATRA对p38含量无明显影响，但磷酸化p38含量明显增加（P < 0.01）。ATRA激活mTOR信号通路（P < 0.05）。总之，这些结果表明，ATRA在调节绵羊成肌细胞增殖和肌分化中起着重要作用，并建议维生素A作为操纵绵羊肌肉生长效率的潜在靶点。(C)2019爱思唯尔公司All rights reserved.
Vitamin A and its metabolite, retinoic acid (RA), play key roles in cell differentiation and organ morphogenesis. The objective of this study was to investigate the effect of RA on sheep primary myoblast proliferation and differentiation. Sheep primary myoblasts were isolated and treated with all-trans retinoic acid (ATRA, 10 nM and 100 nM) and vehicle. The results showed that 10 nM ATRA sufficiently inhibited cell proliferation, which might be through downregulation of cyclin D1 (P < 0.05) and cyclin-dependent kinase 4 (P < 0.05) and proliferating cell nuclear antigen protein (P < 0.05) abundance. Moreover, compared with control cells, both 10 nM and 100 nM ATRA promoted myotube formation and increased fusion index (P < 0.05), which was associated with elevated myogenin mRNA content (P < 0.05). As expected, both myogenin (P < 0.01) and myosin heavy chain (P < 0.05) protein levels were increased by ATRA. Interestingly, ATRA treatment increased H3K4me3 and decreased H3K27me3 enrichment in the myogenin promoter region (P < 0.05). Meanwhile, 100 nM ATRA stimulated 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) Amino)-2-deoxyglucose uptake (P < 0.05) and upregulated glucose transporter 4 expression at both mRNA and protein levels (P < 0.05). Although ATRA did not alter p38 content, phospho-p38 content was increased (P < 0.01). In addition, ATRA treatment activated the mTOR signaling pathway (P < 0.05). Taken together, these results demonstrated that ATRA plays an important role in regulating sheep myoblast proliferation and myogenic differentiation and suggested vitamin A as a potential target for manipulating muscle growth efficiency in sheep industry. (C) 2019 Elsevier Inc. All rights reserved.