Renal developmental defects resulting from in utero hypoxia are associated with suppression of ureteric β-catenin signaling.
Renal developmental defects resulting from in utero hypoxia are associated with suppression of ureteric β-catenin signaling.
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子宫内缺氧导致的肾脏发育缺陷与输尿管 β-连环蛋白信号传导的抑制有关。
作者：
L. Wilkinson;C. Neal;Reetu R. Singh;D. Sparrow;N. Kurniawan;A. Ju;S. Grieve;S. Dunwoodie;K. Moritz;M. Little
妊娠应激源，包括糖皮质激素和蛋白质限制，会影响肾脏发育，从而影响最终肾单位数量。由于缺氧是怀孕期间的常见损伤，因此我们在旨在代表病理性缺氧损伤的模型中研究了氧张力对肾脏发育的影响。开发了中度、短暂、妊娠中期（12% O2，48小时，12.5dpc）或严重、急性、妊娠早期（5.5-7.5% O2，8小时，9.5-10.5dpc）缺氧的体内小鼠模型。已知胚胎本身在缺氧条件下成熟，当母亲暴露于含氧量正常的环境中时，胚胎组织的氧水平估计为 5%-8%（生理性缺氧）。两种体内模型都产生了先天性肾脏和泌尿道异常（CAKUT）患者的表型。严重、急性、早期缺氧导致双肾，而中度、短暂、妊娠中期缺氧永久减少输尿管分支和肾单位形成。两种模型均表现出缺氧诱导的输尿管树内 β-catenin 信号传导减少以及下游靶基因 Ccnd1 的抑制。因此，我们显示了妊娠缺氧和 CAKUT 之间的联系，其表型随着缺氧损伤的时间、持续时间和严重程度而变化。
Gestational stressors, including glucocorticoids and protein restriction, can affect kidney development and hence final nephron number. Since hypoxia is a common insult during pregnancy, we studied the influence of oxygen tension on kidney development in models designed to represent a pathological hypoxic insult. In vivo mouse models of moderate, transient, midgestational (12% O₂, 48 h, 12.5 dpc) or severe, acute, early-gestational (5.5-7.5% O₂, 8 h, 9.5-10.5 dpc) hypoxia were developed. The embryo itself is known to mature under hypoxic conditions with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models generated phenotypes seen in patients with congenital anomalies of the kidney and urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney, while moderate, transient, midgestational hypoxia permanently reduced ureteric branching and nephron formation. Both models displayed hypoxia-induced reductions in β-catenin signaling within the ureteric tree and suppression of the downstream target gene, Ccnd1. Thus, we show a link between gestational hypoxia and CAKUT, the phenotype of which varies with timing, duration, and severity of the hypoxic insult.
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通过大量平行外显子在单侧肾脏发育不全的患者中重新平行候选基因来鉴定两种新型Cakut引起的基因。
影响因子：
19.6
作者：
通讯作者：
--
与 Cited1 缺失相关的胎盘功能不全会导致肾髓质发育不良。
DOI：
10.1681/asn.2008050547
发表时间：
2009
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
--
作者：
Sparrow,DuncanB;Boyle,ScottC;Sams,RebeccaS;Mazuruk,Bogdan;Zhang,Li;Moeckel,GilbertW;Dunwoodie,SallyL;deCaestecker,MarkP
通讯作者：
deCaestecker,MarkP
DOI：
10.1152/ajpregu.00771.2007
发表时间：
2008-08-01
影响因子：
2.8
作者：
Ream, Margie;Ray, Alisa M.;Chikaraishi, Dona M.
通讯作者：
Chikaraishi, Dona M.
DOI：
10.1016/0002-9378(93)90646-z
发表时间：
1993-09-01
影响因子：
9.8
作者：
KAMITOMO, M;ALONSO, JG;GILBERT, RD
通讯作者：
GILBERT, RD
梭曼和缺氧诱导大鼠海马 CA3 锥体神经元急性超微结构改变。
影响因子：
3.4
作者：
Lebeda,FJ;Wierwille,RC;VanMeter,WG;Sikora-VanMeter,KC
通讯作者：
Sikora-VanMeter,KC