Tamura K, Umemura S, Iwamoto T, Yamaguchi S, Kobayashi S, Takeda K, Tokita Y, Takagi N, Murakami K, Fukamizu A
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Hypertension. 1994 Mar;23(3):364-8. doi: 10.1161/01.hyp.23.3.364.
Angiotensinogen gene expression is controlled in a tissue- and development-specific manner. Interestingly, the angiotensinogen gene is abundantly expressed in adipose tissues other than the liver, where it is mainly produced. We investigated the molecular mechanism of angiotensinogen gene expression in a 3T3-L1 preadipocyte-adipocyte system. Although angiotensinogen mRNA was barely detectable in preadipocytes, its levels increased significantly during differentiation. As a whole, the pattern of the change in transcriptional activity of the angiotensinogen promoter was similar to that of the angiotensinogen mRNA levels during adipogenic differentiation, indicating that the activation of the angiotensinogen promoter might be involved in the adipogenic differentiation-coupled gene expression. The proximal promoter region, from -96 to +22 of the transcriptional start site, was sufficient to confer adipogenic activation, and the proximal element from -96 to -52 of the transcriptional start site was necessary for this promoter stimulation. DNA-protein binding experiments showed that this proximal element specifically bound to a nuclear factor induced by adipogenic differentiation. These results suggest that the proximal promoter element from -96 to -52 plays a role in adipogenic activation of the angiotensinogen promoter.
血管紧张素原基因的表达以组织和发育特异性的方式受到调控。有趣的是，血管紧张素原基因在除肝脏（其主要产生部位）之外的脂肪组织中大量表达。我们在3T3-L1前脂肪细胞-脂肪细胞系统中研究了血管紧张素原基因表达的分子机制。尽管在前脂肪细胞中几乎检测不到血管紧张素原mRNA，但其水平在分化过程中显著增加。总体而言，血管紧张素原启动子转录活性的变化模式与成脂分化过程中血管紧张素原mRNA水平的变化模式相似，这表明血管紧张素原启动子的激活可能参与了与成脂分化相关的基因表达。转录起始位点-96至+22的近端启动子区域足以赋予成脂激活作用，转录起始位点-96至-52的近端元件对于该启动子的刺激是必需的。DNA-蛋白质结合实验表明，该近端元件特异性结合由成脂分化诱导的一种核因子。这些结果表明，-96至-52的近端启动子元件在血管紧张素原启动子的成脂激活中发挥作用。
