EFFECT OF IRON ON RENAL TUBULAR EPITHELIAL-CELLS

Since iron has been implicated as a potential nephrotoxin, we examined the effect of iron on several aspects of cultured renal tubular epith elial cell biology. We found that exposure to 10(-4) M of either the f errous or ferric form of iron impaired healing of denuded areas made w ithin confluent monolayers of LLC-PK1 cells. This impairment required 30 to 80 hours of exposure to iron to occur and was also seen in anoth er renal tubular epithelial cell line (MDCK cells). To delineate the p otential mechanism(s) of this impairment, we examined the expression o f a key integrin subunit involved in cell-matrix adhesion. Exposure of LLC-PK1 cells to 10(-4) M ferric citrate for 72 hours significantly d ecreased expression of the beta(1) integrin subunit as determined by f low cytometry. To determine if iron impairs another process that occur s at the basolateral surface, the effects of 72 hours of exposure to i ron on adenylate cyclase activity were examined. Both ferric and ferro us citrate significantly enhanced vasopressin- and forskolin-stimulate d adenylate cyclase activity. To examine if iron can regulate prolifer ation. the effect of iron on H-3-thymidine uptake was measured. We fou nd that ferric citrate diminished proliferation and this decrease requ ired the presence of either serum or transferrin. To ascertain if iron affected ultrastructure, we used transmission electron microscopy and found that iron accumulation within cells was much more apparent with ferric than ferrous citrate, Ferric iron induced mild-to-moderate cyt opathic changes. These results indicate that iron is capable of induci ng multiple changes in renal tubular epithelial function. The effect o f iran to impair wound healing may be related to diminished expression of the beta(1) integrin subunit and perhaps to impaired proliferation .