Regulation of renal tubular cell apoptosis and proliferation after ischemic injury to a solitary kidney

J Lab Clin Med. 2001 Nov;138(5):343-51. doi: 10.1067/mlc.2001.118926.


The time course and regulation of apoptosis and cellular regeneration after 30 minutes of acute ischemic injury to a single kidney was elucidated in rats at five time points over 20 weeks. The fraction of apoptotic cells was most prominent at 1 day after the insult in the distal tubule (8% +/- 4% vs 0% +/- 0%, acute renal failure [ARF] vs sham, respectively) and was still elevated at 7 days (2% +/- 2% vs 0% +/- 0%). At that time, the whole kidney mRNA expression of the apoptosis inhibitory genes bcl-xL and bcl-2, as well as that of the apoptosis promotor bax, was significantly reduced. Immunohistochemistry of kidney specimen showed suppression of bcl-2 in the distal tubule but up-regulation in the proximal tubule, whereas bax protein was more strongly expressed in the distal tubule. Cellular proliferation started at day 1 and continued over the following 20 weeks, leading to severe tubular dilation and kidney failure. These data indicate that differential regulation of bcl-2 family members contributes to the early apoptotic clearance of lethally injured tubular epithelial cells after ischemic injury to a solitary kidney.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Division
  • Ischemia / pathology*
  • Kidney / blood supply*
  • Kidney Tubules / pathology*
  • Male
  • Proliferating Cell Nuclear Antigen / analysis
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein
  • bcl-X Protein


  • Bax protein, rat
  • Bcl2l1 protein, rat
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • bcl-X Protein