Send to

Choose Destination
See comment in PubMed Commons below
Kidney Int. 2002 Nov;62(5):1650-8.

Compensatory renal hypertrophy is mediated by a cell cycle-dependent mechanism.

Author information

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.



Two mechanisms exist for inducing renal proximal tubule hypertrophy. One is characterized by regulation of the G1 cell cycle kinase (cell cycle-dependent mechanism), while the other mechanism involves an imbalance between rates of protein synthesis and degradation, and occurs independently of cell cycle kinase regulation (cell cycle-independent mechanism). The present studies examined whether the compensatory proximal tubule growth following uninephrectomy is mediated by the cell cycle-dependent or -independent mechanism.


Studies were done in both rats and C57Bl6 mice on tissue harvested from sham-operated or uninephrectomized animals. The magnitude of BrdU incorporation was used as the hyperplasia marker, while the proximal tubule protein: DNA ratio was used as the hypertrophy marker. Cdk4/cyclin D and cdk2/cyclin E kinase activities were assayed on renal cortex (rat studies) or isolated proximal tubules (mouse studies) using an in vitro kinase assay.


In both rats and mice, compensatory proximal tubule growth was hypertrophic, not hyperplastic, evidenced by an increase in the protein:DNA ratio without a change in BrdU incorporation. In mice, cdk4/cyclin D kinase activity progressively increased between days 4 and 7, while cdk2/cyclin E kinase activity was decreased at both 4 and 7 days. In rats the development of hypertrophy was associated with an increase in cdk4/cyclin D kinase at days 4, 7, and 10, and an increase in cdk2/cyclin E kinase activity at days 2, 4, and 7. Roscovitine, a cdk2/cyclin E kinase inhibitor, inhibited cdk2/cyclin E kinase activity in both sham and nephrectomized rats; however, it did not prevent the development of proximal tubule hypertrophy.


Uninephrectomy-induced compensatory proximal tubule growth is a hypertrophic form of growth that is mediated by a cell cycle-dependent mechanism.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center