Catanzaro D F, Sun J, Gilbert M T, Yan Y, Black T, Sigmund C, Gross K W
Cardiovascular Center, Cornell University Medical College, New York, New York.
Kidney Int. 1994 Dec;46(6):1513-5. doi: 10.1038/ki.1994.433.
One of the principal aims of our research is to determine the mechanisms which direct renin gene expression to different sites. We recently demonstrated that human renin (hRen) 5'-flanking DNA sequences -148 +/- 11 can drive the transient expression of a linked luciferase reporter gene transfected into pituitary GC cells. This activity was found to be dependent on the binding of Pit-1 to a site approximately 70 bp upstream from the transcription start site. Pit-1 is a pituitary-specific transcription factor which is involved in directing the cell-specific expression of growth hormone (GH) and prolactin (PRL) gene expression to somatotrope and lactotrope cells of the anterior pituitary. Thus, Pit-1 may be play a role in directing the expression of renin to primate lactotrope cells. Renin promoter-driven luciferase or CAT hybrid genes were found to be expressed following transfection into primary, or early passage cell cultures of placental chorionic membranes, and the renin-secreting renal tumor cell line As4.1. As with GC cells, deletion or mutagenesis of the Pit-1 site reduced activity several-fold in both placental and renal cells. These results suggest that members of the POU family of transcription factors, or some other closely related group such as the Hox proteins, participate in directing renin gene expression to placental and juxtaglomerular cells.
我们研究的主要目标之一是确定将肾素基因表达导向不同位点的机制。我们最近证明，人肾素（hRen）5'-侧翼DNA序列-148±11能够驱动转染到垂体GC细胞中的连接荧光素酶报告基因的瞬时表达。发现这种活性依赖于Pit-1与转录起始位点上游约70 bp处的一个位点的结合。Pit-1是一种垂体特异性转录因子，参与将生长激素（GH）和催乳素（PRL）基因表达导向垂体前叶的生长激素细胞和催乳素细胞的细胞特异性表达。因此，Pit-1可能在将肾素表达导向灵长类催乳素细胞中发挥作用。肾素启动子驱动的荧光素酶或CAT杂交基因在转染到胎盘绒毛膜的原代或早期传代细胞培养物以及分泌肾素的肾肿瘤细胞系As4.1后被发现表达。与GC细胞一样，Pit-1位点的缺失或诱变在胎盘和肾细胞中均使活性降低了几倍。这些结果表明，POU家族转录因子成员或其他一些密切相关的组，如Hox蛋白，参与将肾素基因表达导向胎盘和球旁细胞。
