期刊
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 24, 期 3, 页码 433-444出版社
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2012080791
关键词
-
资金
- German Research Foundation (DFG) [SFB 699]
States of low perfusion pressure of the kidney associate with hyperplasia or expansion of renin-producing cells, but it is unknown whether hypoxia-triggered genes contribute to these changes. Here, we stabilized hypoxia-inducible transcription factors (HIFs) in mice by conditionally deleting their negative regulator, Vhl, using the Cre/loxP system with renin-1d promoter-driven Cre expression. Vhl(-/-REN) mice were viable and had normal BP. Deletion of Vhl resulted in constitutive accumulation of HIF-2 alpha in afferent arterioles and glomerular cells and HIF-1 alpha in collecting duct cells of the adult kidney. The preglomerular vascular tree developed normally, but far fewer renin-expressing cells were present, with more than 70% of glomeruli not containing renin cells at the typical juxtaglomerular position. Moreover, these mice had an attenuated expansion of renin-producing cells in response to a low-salt diet combined with an ACE inhibitor. However, renin-producing cells of Vhl(-/-REN) mice expressed the erythropoietin gene, and they were markedly polycythemic. Taken together, these results suggest that hypoxia-inducible genes, regulated by VHL, are essential for normal development and physiologic adaptation of renin-producing cells. In addition, deletion of Vhl shifts the phenotype of juxtaglomerular cells from a renin- to erythropoietin-secreting cell type, presumably in response to HIF-2 accumulation. J Am Soc Nephrol 24: 433-444, 2013. doi: 10.1681/ASN.2012080791
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据