Effect of oxidant stress on growth factor stimulation of proliferation in cultured human proximal tubule cells.

Abstract

Restoring kidney function after injury involves cell migration and proliferation, processes that are yet to be precisely defined. Because epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) promote recovery from acute renal failure, we used SV-40 immortalized human proximal tubule cells to examine the effects of these growth factors on cell proliferation after peroxide injury (1.5 mM for 1 hour). ATP levels decreased to approximately 15% of control values immediately after injury but returned to nearly normal levels after 4 hours of recovery. Under control conditions, both EGF and IGF-1 stimulated proliferation and their effects were additive. However, 20-24 hours after injury, while IGF-1 stimulated proliferation, EGF was no longer effective nor was the combination of EGF and IGF-1. Although the EGF receptor was decreased 20 hours after injury, the lack of IGF-1 effect could not be explained by loss of the IGF-1 receptor, which remained unchanged after peroxide injury. Thus, the mechanism responsible for the blunting of the IGF-1 effect on proliferation following injury remains speculative. However, we conclude that the effects of growth factors under control conditions may not predict their effects after injury.