title: 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.
authors.affiliation: Department of Medicine, Tulane University School of Medicine and the Veterans Administration Hospital, New Orleans, Louisiana 70115, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Weston
authors.forename: M B
authors.initials: MB
authors.lastname: Feibelman
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: E E
authors.initials: EE
authors.lastname: Simon
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D004815:Epidermal Growth Factor