Department of Women's and Children's Health, Karolinska Institutet, Stockholm 17176, Sweden.
Nat Commun. 2010 Jul 27;1(4):42. doi: 10.1038/ncomms1043.
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.
肾脏对胎儿发育不良极为敏感。营养不良是最常见的发育挑战形式，它会阻碍功能单位（肾单位）的形成。由此导致的低肾单位数增加了肾脏损伤和疾病的易感性。通过对离体的大鼠胚胎肾脏进行研究，我们发现哇巴因（Na,K-ATPase 配体）会引发钙核因子-κB 信号，从而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，我们将肾脏的血清剥夺 24 小时。这导致肾单位形成严重滞后，细胞凋亡显著增加。而在哇巴因暴露的肾脏中，没有观察到血清剥夺的不良影响。从对给予低蛋白饮食的怀孕大鼠的研究中获得了哇巴因挽救暴露于营养不良的胚胎肾脏发育的原理证明，并对其进行了哇巴因或载体治疗的处理。因此，我们已经确定了一种生存信号和一种可行的治疗工具，可以预防肾脏发育的不良编程。
