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

Signaling by urea, although incompletely understood, is relevant both to cells 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 stress are distinct from those occurring in response to hypertonic stress; urea activates a characteristic subset of signaling events, which are in large 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 likened to that of either hypertonicity or of a peptide mitogen. In preliminary expression array analyses, the profile of genes activated by urea stress in renal medullary cells, however, was found to be unique.