期刊
PEDIATRIC RESEARCH
卷 67, 期 6, 页码 573-578出版社
NATURE PUBLISHING GROUP
DOI: 10.1203/PDR.0b013e3181da477c
关键词
-
类别
资金
- NIH [P20 RRI7659, DK-71699]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR017659] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK071699] Funding Source: NIH RePORTER
Mutations in the genes encoding components of the renin-angiotensin system (RAS) in mice or humans cause congenital abnormalities of the kidney and urinary tract. We hypothesized that absence of angiotensin (Ang) II in angiotensinogen (AGT)-deficient mice leads to defects in ureteric bud (UB) branching and that RAS genes are critically dependent on histone deacetylase (HDAC) activity. The number of UB tips was lower in AGT(-/-) compared with AGT(+/+) embryonic (E) day E13.5 metanephroi (24 +/- 1.5 versus 36 +/- 3.7, p < 0.05). Real-time RT-PCR demonstrated that pharmacological inhibition of HDAC activity with Scriptaid increases AGT, renin, angiotensin-converting enzyme (ACE), and AT(1) receptor (AT(1)R) mRNA levels in E12.5 mouse metanephroi and early mesenchymal (MK3) cells. Furthermore, Scriptaid enhanced Ang II-induced decrease in Sprouty (Spry) I gene expression in cultured UB cells. Treatment of intact E12.5 mouse metanephroi grown ex vivo with Ang II (10(-5) M, 24 h) increased HDAC-I and decreased total acetylated histone H3 protein levels. These findings indicate that lack of endogenous Ang II in AGT-deficient mice inhibits UB branching. We conclude that intact RAS is critical in structural integrity of the renal collecting system and that UB morphogenetic program genes, such as AGT, renin, ACE, AT(1)R, or Spry1, are epigenetically controlled via HDACs. (Pediatr Res 67: 573-578, 2010)
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