Ouabain protects against adverse developmental programming of the kidney
2010 (English)In: Nature communications, ISSN 2041-1723, Vol. 1, 42- p.Article in journal (Refereed) Published
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-kappa B 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.
Place, publisher, year, edition, pages
2010. Vol. 1, 42- p.
NA-K-ATPASE, NF-KAPPA-B, PROXIMAL TUBULAR CELLS, LOW-BIRTH-WEIGHT, CALCIUM OSCILLATIONS, RENAL-DISEASE, GLOMERULAR NUMBER, HYPERTENSION, NEPHRON, RESTRICTION
Medical and Health Sciences Condensed Matter Physics
IdentifiersURN: urn:nbn:se:kth:diva-27063DOI: 10.1038/ncomms1043ISI: 000283645000009ScopusID: 2-s2.0-84880276667OAI: oai:DiVA.org:kth-27063DiVA: diva2:376677
QC 201012132010-12-132010-12-062010-12-13Bibliographically approved