Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
J Am Soc Nephrol. 2010 Mar;21(3):460-7. doi: 10.1681/ASN.2009090964. Epub 2010 Jan 7.
Juxtaglomerular cells are highly specialized myoepithelioid granulated cells located in the glomerular afferent arterioles. These cells synthesize and release renin, which distinguishes them from other cells. How these cells maintain their identity, restricted localization, and fate is unknown and is fundamental to the control of BP and homeostasis of fluid and electrolytes. Because microRNAs may control cell fate via temporal and spatial gene regulation, we generated mice with a conditional deletion of Dicer, the RNase III endonuclease that produces mature microRNAs in cells of the renin lineage. Deletion of Dicer severely reduced the number of juxtaglomerular cells, decreased expression of the renin genes (Ren1 and Ren2), lowered plasma renin concentration, and decreased BP. As a consequence of the disappearance of renin-producing cells, the kidneys developed striking vascular abnormalities and prominent striped fibrosis. We conclude that microRNAs maintain the renin-producing juxtaglomerular cells and the morphologic integrity and function of the kidney.
球旁细胞是位于肾小球入球小动脉的高度特化的肌上皮样颗粒细胞。这些细胞合成并释放肾素，这使它们有别于其他细胞。这些细胞如何维持其身份、受限的定位和命运尚不清楚，这对于控制血压和体液及电解质的内环境稳定至关重要。由于 microRNAs 可以通过时间和空间的基因调控来控制细胞命运，我们生成了 Dicer 条件性缺失的小鼠，Dicer 是一种 RNase III 内切酶，可在肾素谱系细胞中产生成熟的 microRNAs。Dicer 的缺失严重减少了球旁细胞的数量，降低了肾素基因（Ren1 和 Ren2）的表达，降低了血浆肾素浓度，降低了血压。由于产生肾素的细胞消失，肾脏出现了明显的血管异常和明显的条纹纤维化。我们的结论是，microRNAs 维持着产生肾素的球旁细胞以及肾脏的形态完整性和功能。
