Signaling and gene regulation by urea in cells of the mammalian kidney medulla

Signaling by urea, although incompletely understood, is relevant both to ce lls of the mammalian kidney inner medulla and to all cells of the organism in the setting of advanced renal failure with its attendant accumulation of urea in the systemic circulation. The molecular events initiated by urea s tress are distinct from those occurring in response to hypertonic stress; u rea. activates a characteristic subset of signaling events, which are in la rge part specific to cultured renal tubular epithelial cells. Interestingly , urea is protective of hypertonic NaCl-inducible apoptosis in this model. Details of this phenomenon are reviewed. The effect of urea has been likene d to that of either hypertonicity or of a peptide mitogen. In preliminary e xpression array analyses, the profile of genes activated by urea stress in renal medullary cells, however, was found to be unique. (C) 2001 Elsevier S cience Inc. All rights reserved.