Fraser J D, Keller D, Martinez V, Santiso-Mere D, Straney R, Briggs M R
Ligand Pharmaceuticals Inc., San Diego, California 92121, USA.
J Biol Chem. 1997 May 23;272(21):13892-8. doi: 10.1074/jbc.272.21.13892.
Using recombinant adenoviral vectors and a dominant negative mutant of HNF-4, we have examined the contribution of hepatocyte nuclear factor 4 (HNF-4) to endogenous apolipoprotein AI and CIII mRNA expression. Overexpression of HNF-4 leads to a 7.4-fold increase in apolipoprotein CIII expression, while infection with the dominant negative mutant of HNF-4 reduces the level of apolipoprotein CIII mRNA by 80%, demonstrating that endogenous HNF-4 is necessary for apolipoprotein CIII expression. Experiments using the hepatoma cell lines, HepG2 and Hep3B, indicate that HNF-4 is also involved in the regulation of apolipoprotein AI expression in these lines. However, the effect of HNF-4 on apolipoprotein AI expression is much more dramatic in cell lines derived from intestinal epithelium. Infection of the intestinal-derived cell line IEC-6 with the HNF-4 adenovirus resulted in a greater than 20-fold increase in the level of apolipoprotein AI mRNA. These results indicate that HNF-4 does regulate apolipoprotein AI and CIII mRNA expression and suggest that HNF-4 is critical for intestinal apolipoprotein AI expression.
利用重组腺病毒载体和肝细胞核因子4（HNF-4）的显性负性突变体，我们研究了肝细胞核因子4（HNF-4）对内源性载脂蛋白AI和CIII mRNA表达的作用。HNF-4的过表达导致载脂蛋白CIII表达增加7.4倍，而用HNF-4的显性负性突变体感染则使载脂蛋白CIII mRNA水平降低80%，表明内源性HNF-4是载脂蛋白CIII表达所必需的。使用肝癌细胞系HepG2和Hep3B进行的实验表明，HNF-4也参与了这些细胞系中载脂蛋白AI表达的调控。然而，HNF-4对载脂蛋白AI表达的影响在源自肠上皮的细胞系中更为显著。用HNF-4腺病毒感染源自肠道的细胞系IEC-6，导致载脂蛋白AI mRNA水平增加超过20倍。这些结果表明，HNF-4确实调节载脂蛋白AI和CIII mRNA的表达，并提示HNF-4对肠道载脂蛋白AI的表达至关重要。
