Wagner Nicole, Wagner Kay-Dietrich, Scholz Holger, Kirschner Karin M, Schedl Andreas
Institut National de la Santé et de la Recherche Médicale U636, Centre de Biochimie, Faculté des Sciences, Université de Nice, 06108 Nice, France.
Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R779-87. doi: 10.1152/ajpregu.00219.2006. Epub 2006 Apr 13.
Nestin is an intermediate filament protein originally described in neural stem cells and a variety of progenitor cells. More recently, nestin was detected in rat kidney podocytes. We show here that nestin is expressed in a developmentally regulated pattern in the kidney. Nestin was detected by immunohistochemistry in the condensing mesenchyme surrounding the ureter, in developing glomeruli, in podocytes of the adult kidney, and in a podocyte cell line. Nestin shared a striking overlap in expression with the Wilms' tumor suppressor Wt1. Nestin was significantly upregulated in a cell line with inducible Wt1 expression upon induction of Wt1. Cotransfection experiments in human embryonic kidney cells (HEK293) revealed stimulation of a nestin intron 2 enhancer element up to six-fold by the Wt1(-KTS) splice variant. Nestin expression was significantly reduced in an inducible mouse model of glomerular disease. This model is based on podocyte-specific overexpression of Pax2 and associated with a loss of Wt1 expression. Furthermore, also in the developing heart, nestin was found in an overlapping pattern with Wt1 in the epicardium and the forming coronary vessels. Strikingly, in the hearts of Wt1 knockout mice, nestin was barely detectable compared with the hearts of wild-type embryos. Our results show that nestin is expressed at different stages of kidney and cardiac development and suggest that its expression in these organs might be regulated by the Wilms' tumor suppressor Wt1.
巢蛋白是一种中间丝蛋白，最初在神经干细胞和多种祖细胞中被描述。最近，在大鼠肾足细胞中检测到了巢蛋白。我们在此表明，巢蛋白在肾脏中以发育调控的模式表达。通过免疫组织化学在输尿管周围的凝聚间充质、发育中的肾小球、成年肾脏的足细胞以及一种足细胞系中检测到了巢蛋白。巢蛋白在表达上与肾母细胞瘤抑制因子Wt1有显著重叠。在一个可诱导Wt1表达的细胞系中，诱导Wt1后巢蛋白显著上调。在人胚肾细胞（HEK293）中的共转染实验显示，Wt1（-KTS）剪接变体可将巢蛋白内含子2增强子元件的刺激作用提高至6倍。在一个可诱导的肾小球疾病小鼠模型中巢蛋白表达显著降低。该模型基于足细胞特异性过表达Pax2并伴有Wt1表达缺失。此外，同样在发育中的心脏，在心外膜和形成中的冠状血管中发现巢蛋白与Wt1的表达模式重叠。引人注目的是，与野生型胚胎的心脏相比，在Wt1基因敲除小鼠的心脏中几乎检测不到巢蛋白。我们的结果表明，巢蛋白在肾脏和心脏发育的不同阶段表达，并提示其在这些器官中的表达可能受肾母细胞瘤抑制因子Wt1调控。
