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Ouabain protects against adverse developmental programming of the kidney

Author

Listed:
  • Juan Li

    (Karolinska Institutet)

  • Georgiy R. Khodus

    (Karolinska Institutet)

  • Markus Kruusmägi

    (Karolinska Institutet)

  • Padideh Kamali-Zare

    (Royal Institute of Technology)

  • Xiao-Li Liu

    (Karolinska Institutet)

  • Ann-Christine Eklöf

    (Karolinska Institutet)

  • Sergey Zelenin

    (Karolinska Institutet)

  • Hjalmar Brismar

    (Karolinska Institutet
    Royal Institute of Technology)

  • Anita Aperia

    (Karolinska Institutet)

Abstract

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.

Suggested Citation

  • Juan Li & Georgiy R. Khodus & Markus Kruusmägi & Padideh Kamali-Zare & Xiao-Li Liu & Ann-Christine Eklöf & Sergey Zelenin & Hjalmar Brismar & Anita Aperia, 2010. "Ouabain protects against adverse developmental programming of the kidney," Nature Communications, Nature, vol. 1(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:1:y:2010:i:1:d:10.1038_ncomms1043
    DOI: 10.1038/ncomms1043
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