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

Liu, Baolian; Preisig, Patricia A.

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

KIDNEY hypertrophy; CELL cycle; PROTEIN metabolism; PHYSIOLOGICAL adaptation; ANIMAL experimentation; CELL physiology; COMPARATIVE studies; ENZYME inhibitors; HYPERTROPHY; KIDNEY tubules; RESEARCH methodology; MEDICAL cooperation; MICE; PROTEIN kinases; PROTEINS; PURINES; RATS; RESEARCH; EVALUATION research; NEPHRECTOMY; PROTEIN kinase inhibitors; PHARMACODYNAMICS

Kidney International, 2002, Vol 62, Issue 5, p1650

0085-2538

Academic Journal

10.1046/j.1523-1755.2002.00620.x