Retinoic acid affects the cell cycle and increases total protein content in epithelial cells

Retinoids and particularly retinoic acid (RA) have been incriminated in the adaptation to uninephrectomy and compensatory kidney growth in humans. However, there is no data assessing the effects of RA on renal cells. Since the bulk of the compensatory kidney growth is due to tubular cells, we studied the effects of RA, retinol and epidermal growth factor (EGF) on a rabbit kidney epithelial cell line RK13 in culture. RA significantly increased thymidine incorporation by 42 +/- 8% (P less than 0.01). This increase appeared as soon as three hours after adding RA and could still be observed after five days. Total protein content was also increased by RA by 37 +/- 4% (P less than 0.01). Flow cytometer analysis showed a significant decrease in the percentage of resting cells (G0-G1 phases) induced by RA (-9.4 +/- 2%; P less than 0.01). We observed similar results in growth factor free medium, and the RA induced changes were the same in confluent and non-confluent cells. Retinol did not modify thymidine incorporation or total protein content. EGF increased by 75% thymidine incorporation (P less than 0.01). In serum free conditions RA failed to have a synergistic effect with EGF. These data show that RA is able to induce modifications in kidney epithelial cells compatible with those observed in hypertrophy while retinol is not. These modifications are not due to other growth factor potentiation but to RA itself, and are independent of the contact-inhibition phenomenon.