Urea selectively induces DNA synthesis in renal epithelial cells

D. M. Cohen, S. R. Gullans

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Hyperosmotic stress with the functionally impermeant solute NaCl has been shown by us and others to inhibit cell growth and DNA synthesis. Several lines of evidence suggest that urea, the other principal renal medullary solute, may exert a growth-promoting effect on renal epithelial cells. Among these is the finding that urea upregulates expression at the mRNA level of two growth-associated immediate-early genes, Egr-1 and c-fos. In the present study, urea, in concentrations characteristic of the renal medulla, increased [3H]thymidine incorporation approximately threefold in confluent, growth- suppressed Madin-Darby canine kidney (MDCK) cells, whereas another readily membrane-permeant solute, glycerol, did not. Urea also overcame the inhibitory effect of hyperosmotic NaCl on DNA synthesis. The urea-induced increase in [3H]thymidine incorporation was also evident in the renal epithelial LLC-PK1 cell line, but not in renal nonepithelial and epithelial nonrenal cell types examined. In addition, it was associated with a 15% increase in total DNA content measured fluorometrically at 24 h of treatment. There was, however, no associated increase in cell proliferation as measured by cell number, total protein content, or cell cycle distribution. Urea also failed to induce polyploidy or aneuploidy. Therefore cells of renal epithelial origin may be uniquely capable of responding to hyperosmotic urea with increased DNA synthesis through an undefined and potentially novel mechanism.

Original languageEnglish (US)
Pages (from-to)F601-F607
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number4 33-4
StatePublished - 1993
Externally publishedYes


  • LLC-PK
  • Madin-Darby canine kidney
  • cell cycle
  • glycerol
  • hyperosmotic stress
  • osmoregulation
  • sodium chloride

ASJC Scopus subject areas

  • Physiology


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