Effects on hepatic lipid metabolism in human hepatoma cells following overexpression of TGFβ induced factor homeobox 1 or 2
Effects on hepatic lipid metabolism in human hepatoma cells following overexpression of TGFβ induced factor homeobox 1 or 2
复制标题
DOI：
10.1016/j.bbalip.2019.02.009
复制
发表时间：
2019-05-01
影响因子：
4.8
通讯作者：
Pramfalk, Camilla
中科院分区：
文献类型：
--
作者：
Hardfeldt, Jennifer;Hodson, Leanne;Pramfalk, Camilla
转化生长因子β诱导因子同源框（Transforming growth factor beta induced factor homeobox，TGIF）1和2是两种转录抑制因子。尽管已经发现TGF 1参与脂质代谢，但是还没有研究调查TGF 2在肝脏脂质代谢中的作用。在这里，我们的目的是研究人类和小鼠TGF-1和TGF-2蛋白过表达对肝脏脂质代谢的影响。我们使用修饰的mRNA分子瞬时增强这些蛋白在人肝癌细胞中的表达。我们发现所有的mRNA分子都被翻译，除了人TGIF 1。瞬时转染小鼠TGF 1 mRNA分子可使细胞培养基中胆固醇（p < 0.001）、甘油三酯（p < 0.001）和载脂蛋白B（p < 0.05）的水平降低约40%，同时沿着的还有一些参与脂质代谢的关键基因的mRNA水平。相反，在用人和小鼠TGIF 2 mRNA分子瞬时转染后观察到对这些参数的有限影响。为了能够研究增强人TGIF 1蛋白表达后的效果，我们在人肝癌细胞中稳定过表达该蛋白。与上述发现一致，我们发现稳定过表达人TGF 1蛋白的细胞在细胞培养基中胆固醇（p < 0.05）、甘油三酯（p < 0.05）和载脂蛋白B（p < 0.05）的水平降低了约30%。因此，瞬时和稳定的过表达的TGIF 1蛋白似乎导致一个有利的脂质谱。
Transforming growth factor beta induced factor homeobox (TGIF) 1 and 2 are two transcriptional repressors. Although TGIF1 has been found to be involved in lipid metabolism, no studies have yet investigated the role of TGIF2 in hepatic lipid metabolism. Here we aim to investigate effects on hepatic lipid metabolism following overexpression of the human and mouse TGIF1 and TGIF2 protein. We used modified mRNA molecules to transiently enhance the expression of these proteins in human hepatoma cells. We found all the mRNA molecules to be translated, except the one for human TGIF1. Transient transfection with the mouse TGIF1 mRNA molecules lowered levels of cholesterol (p < 0.001), triglycerides (p < 0.001), and apolipoprotein B (p < 0.05) in the cell media by similar to 40%, along with the mRNA levels of some key genes involved in lipid metabolism. In contrast, limited effects on these parameters were observed following transient transfection with the human and mouse TGIF2 mRNA molecules. To enable investigation of the effects following enhanced expression of the human TGIF1 protein, we stably overexpressed this protein in human hepatoma cells. In line with the above findings, we found cells stably overexpressing the human TGIF1 protein had lower levels of cholesterol (p < 0.05), triglycerides (p < 0.05) and apolipoprotein B (p < 0.05) in the cell media by similar to 30%. Hence, transient and stable overexpression of the TGIF1 protein appears to lead to an advantageous lipid profile.