Effects of EGF and IGF-1 on proliferation of cultured human proximal tubule cells after oxidant stress

Background. Both insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) stimulate proliferation of various renal tubule epithelial cells in culture including proximal tubule cells. In some epithelial cells, the effects of EGF and IGF-1 are additive or synergistic. The effects of EGF and IGF-1 I in cultured tubule epithelial cells following injury are limited. Methods. Immortalized human proximal tubules cultured in serum-free defined medium were exposed to 0.3-1.5 mM peroxide for I It then washed and growth factors were added. ATP was measured by chemiluminescence, proliferation by [H-3]thymidine uptake, and receptor expression by flow cytometry. Results. Immediately after 1.5 mM peroxide exposure, ATP levels were depressed to as low as similar to15% of normal but had recovered to near normal levels by 4 h. Proliferation was depressed in a dose-dependent manner by peroxide. At the lowest doses of peroxide both EGF (20 ng/mL) and IGF-1 (390 ng/mL) stimulated proliferation. As the concentration of peroxide increased, EGF lost its ability to stimulate proliferation and in fact antagonized IGF-1 which when added alone remained effective at stimulating proliferation even at the highest levels of peroxide exposure. EGF and peroxide depressed EGF receptor expression but there were no changes in IGF-1 receptor expression with any maneuver. Conclusion. The effects of EGF to antagonize IGF-1 are distal to IGF-1 receptor expression. The effects of these growth factors under control conditions do no translate to effects after injury.