Ouabain protects against adverse developmental programming of the kidney.
Ouabain protects against adverse developmental programming of the kidney.
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哇巴因可防止肾脏发育不良。
DOI：
10.1038/ncomms1043
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发表时间：
2010-07-27
影响因子：
16.6
通讯作者：
Aperia, Anita
中科院分区：
文献类型：
--
作者：
Li, Juan;Khodus, Georgiy R.;Kruusmagi, Markus;Kamali-Zare, Padideh;Liu, Xiao-Li;Eklof, Ann-Christine;Zelenin, Sergey;Brismar, Hjalmar;Aperia, Anita
肾脏对不良的胎儿程序化特别敏感。营养不良是最常见的发育挑战形式，它会阻碍肾单位功能单位的形成。由此导致的低肾单位捐赠增加了肾脏损伤和疾病的易感性。使用移植的大鼠胚胎肾脏，我们发现哇巴因，Na，K-κ酶配体，触发钙-核因子-ATP B信号，保护肾脏发育免受营养不良的不利影响。为了模拟营养不良，肾脏的血清被剥夺24小时。这导致肾单位的形成严重受阻，细胞凋亡率显著增加。在哇巴因暴露的肾脏中，没有观察到血清剥夺的不良影响。哇巴因挽救暴露在营养不良中的胚胎肾脏发育的原理证据是从对怀孕大鼠的研究中获得的，这些研究给予低蛋白饮食，并在怀孕期间使用哇巴因或赋形剂治疗。因此，我们已经确定了一个生存信号和一个可行的治疗工具，以防止肾脏发育的不利编程。众所周知，母亲营养不良会影响胎儿肾脏的发育。这项研究表明，钠钾ATPase配体哇巴因在体外可以保护肾脏免受血清饥饿引起的细胞死亡，以及在体内保护肾脏免受低蛋白饮食导致的异常肾脏发育。
The kidney is extraordinarily sensitive to adverse fetal programming. Malnutrition, the most common form of developmental challenge, retards the formation of functional units, the nephrons. The resulting low nephron endowment increases susceptibility to renal injury and disease. Using explanted rat embryonic kidneys, we found that ouabain, the Na,K-ATPase ligand, triggers a calcium–nuclear factor-κB signal, which protects kidney development from adverse effects of malnutrition. To mimic malnutrition, kidneys were serum deprived for 24 h. This resulted in severe retardation of nephron formation and a robust increase in apoptosis. In ouabain-exposed kidneys, no adverse effects of serum deprivation were observed. Proof of principle that ouabain rescues development of embryonic kidneys exposed to malnutrition was obtained from studies on pregnant rats given a low-protein diet and treated with ouabain or vehicle throughout pregnancy. Thus, we have identified a survival signal and a feasible therapeutic tool to prevent adverse programming of kidney development. Poor maternal nutrition is known to affect fetal kidney development. This study shows that the sodium potassium ATPase ligand, ouabain, protects kidneys from cell death induced by serum starvation in vitro and from abnormal kidney development due to a low-protein diet in vivo.
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影响因子：
3.2
作者：
Nuyt AM;Alexander BT
通讯作者：
Alexander BT
影响因子：
13.6
作者：
Dziarmaga, Alison;Eccles, Michael;Goodyer, Paul
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Goodyer, Paul
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SANYANUSIN, P;SCHIMMENTI, LA;ECCLES, MR
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作者：
APERIA, A;LARSSON, L;ZETTERSTROM, R
通讯作者：
ZETTERSTROM, R
影响因子：
11.1
作者：
Aperia, A.
通讯作者：
Aperia, A.