Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, USA.
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, USA.
Kidney Int. 2012 May;81(10):993-1001. doi: 10.1038/ki.2011.463. Epub 2012 Jan 25.
The kidney is the major, if not sole, site for the production of 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the biologically active form of vitamin D that can stimulate calcium reabsorption in the kidney and may provide renoprotective benefits. The biological effects of 1,25(OH)(2)D(3) are mediated through a nuclear hormone receptor, known as the vitamin D receptor (VDR). It is well accepted that the VDR is present in the distal renal convoluted tubule cells; however, whether VDR is present in other kidney cell types is uncertain. Using a highly specific and sensitive anti-VDR antibody, we determined its distribution in the mouse kidney by immunohistochemistry. Our results show that the VDR is not only present in the distal but is also found in the proximal tubules, but at 24-fold lower levels. The VDR was also found in the macula densa of the juxtaglomerular apparatus, glomerular parietal epithelial cells, and podocytes. In contrast, the VDR is either very low or absent in interstitial fibroblasts, glomerular mesangial cells, and juxtaglomerular cells. Thus, identification of VDR in the proximal tubule, macula densa, and podocytes suggests that 1,25(OH)(2)D(3) plays a direct role in these cells under normal conditions.
肾脏是 1α,25-二羟维生素 D(3)(1,25(OH)(2)D(3))产生的主要(如果不是唯一)部位,1,25(OH)(2)D(3)是维生素 D 的生物活性形式,可刺激肾脏对钙的重吸收,并可能提供肾脏保护作用。1,25(OH)(2)D(3)的生物学效应是通过一种核激素受体,即维生素 D 受体(VDR)介导的。人们普遍认为 VDR 存在于远端肾曲管细胞中;然而,VDR 是否存在于其他肾脏细胞类型中尚不确定。我们使用高度特异性和敏感的抗 VDR 抗体,通过免疫组织化学方法确定了 VDR 在小鼠肾脏中的分布。结果表明,VDR 不仅存在于远端肾曲管,也存在于近端肾小管,但水平低 24 倍。VDR 还存在于肾小球旁器的致密斑、肾小球壁细胞和足细胞中。相比之下,VDR 在间质成纤维细胞、肾小球系膜细胞和肾小球旁细胞中含量很低或不存在。因此,在近端肾小管、致密斑和足细胞中鉴定出 VDR 表明,在正常条件下,1,25(OH)(2)D(3)在这些细胞中发挥直接作用。