MiR-183 promotes preadipocyte differentiation by suppressing Smad4 in goats
MiR-183 promotes preadipocyte differentiation by suppressing Smad4 in goats
复制标题
MiR-183 通过抑制山羊中的 Smad4 促进前脂肪细胞分化
DOI：
10.1016/j.gene.2018.05.022
复制
发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Zhang Hongping
中科院分区：
文献类型：
--
作者：
Zhao Wei;Yang Hailong;Li Juntao;Chen Yuan;Cao Jiaxue;Zhong Tao;Wang Linjie;Guo Jiazhong;Li Li;Zhang Hongping
作为一种高度保守的 microRNA，miR-183 在许多组织和细胞中普遍表达，包括背膘和 3T3-L1 脂肪细胞。然而，人们对 miR-183 在脂肪生成中的调节机制仍知之甚少。在这里，我们利用水鹿前脂肪细胞探讨了 miR-183 在脂肪生成中的表达模式和作用。结果表明，miR-183在前脂肪细胞分化过程中上调，miR-183的过表达增强了脂质积累，并显着增加了脂肪形成基因PPARγ、C/EBPα、SREBP-1c、FAS和ACC的mRNA表达。使用生物信息学工具，我们预测 Smad4 是 miR-183 的靶标。随后通过荧光素酶报告基因测定验证了这一点。 miR-183的过表达显着抑制Smad4的mRNA和蛋白水平，而抑制miR-183则具有相反的效果。然而，抑制Smad4会大大加速脂质沉积并增加脂肪形成基因的表达，这与miR-183过表达的结果一致。总之，这些结果表明 miR-183 通过靶向 Smad4 促进水牛前脂肪细胞分化。
As a well-conserved microRNA, miR-183 is ubiquitously expressed in many tissues and cells including backfat and the 3T3-L1 adipocytes; however, the mechanisms regulating miR-183 in adipogenesis remain poorly understood. Here, we explored the expression pattern and role of miR-183 in adipogenesis using hircine preadipocytes. The results showed that miR-183 was up-regulated during preadipocyte differentiation, and overexpression of miR-183 enhanced lipid accumulation and dramatically increased the mRNA expression of the adipogenic genesPPARγ,C/EBPα,SREBP-1c,FAS, andACC. Using bioinformatics tools, we predictedSmad4to be a target of miR-183. This was subsequently validated with a luciferase reporter assay. Overexpression of miR-183 suppressed the mRNA and protein levels ofSmad4significantly, whereas inhibiting miR-183 had the opposite effect. However, inhibition ofSmad4greatly accelerated lipid deposition and increased the expression of adipogenic genes which consists with the results of miR-183 overexpression. In conclusion, these results indicate that miR-183 promotes hircine preadipocyte differentiation by targetingSmad4.