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OUABAIN RESCUES NEPHROGENESIS IN GROWTH‐FACTOR DEPRIVED EMBRYONIC RAT KIDNEY
Author(s) -
Li Juan,
Perini Ilaria,
KRUUSMÄGI MARKUS,
AIZMAN OLEG,
ZELENIN SERGEY,
aperia anita
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1157.7
Subject(s) - ouabain , endocrinology , medicine , signal transduction , microbiology and biotechnology , apoptosis , calcium in biology , calcium , biology , kidney , stimulation , nephron , intracellular , chemistry , biochemistry , organic chemistry , sodium
Fetal malnutrition and other factors contributing to renal growth retardation result in increased apoptosis and reduction in nephron endowment. Our group has described a novel signaling pathway, where direct interaction between Na,K‐ATPase (NKA) and IP3R triggers slow calcium oscillations and activation of NFkappaB (PNAS 2001, JBC 2003, 2006). This signaling pathway is activated by ouabain, a specific ligand of NKA. Downstream effects include protection from apoptosis and stimulation of cell proliferation (JASN 2006). Here we report activation of this signaling pathway rescues nephrogenesis in growth factor deprived (gfd) embryonic rat kidney. Kidneys from E14 rats were cultured under normal or gfd conditions and studied after 2–3 days in vitro. Exposure to ouabain triggered calcium oscillation and activated NF‐kappaB. Growth factor deprivation retarded ureter branching and formation of new glomeruli and increased apoptotic index. Exposure to nM ouabain prevented these effects. The protective effects of ouabain were abolished by depletion of intracellular calcium stores and by inhibition of NF‐kappaB, underlining the importance of the NKA‐IP3R signaling pathway. The expression of Wt1 and Pax2, which are activated by NF‐kappaB, was increased in ouabain exposed gfd kidneys. Thus we have identified a novel mechanism by which kidney development can be protected under adverse intrauterine circumstances.