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 epithelial cell biology. We found that exposure to 10(-4) M of either the ferrous or ferric form of iron impaired healing of denuded areas made within confluent monolayers of LLC-PK1 cells. This impairment required 30 to 80 hours of exposure to iron to occur and was also seen in another renal tubular epithelial cell line (MDCK cells). To delineate the potential mechanism(s) of this impairment, we examined the expression of a key integrin subunit involved in cell-matrix adhesion. Exposure of LLC-PK1 cells to 10(-4) M ferric citrate for 72 hours significantly decreased expression of the beta 1 integrin subunit as determined by flow cytometry. To determine if iron impairs another process that occurs at the basolateral surface, the effects of 72 hours of exposure to iron on adenylate cyclase activity were examined. Both ferric and ferrous citrate significantly enhanced vasopressin- and forskolin-stimulated adenylate cyclase activity. To examine if iron can regulate proliferation, the effect of iron on 3H-thymidine uptake was measured. We found that ferric citrate diminished proliferation and this decrease required 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 cytopathic changes. These results indicate that iron is capable of inducing multiple changes in renal tubular epithelial function. The effect of iron to impair wound healing may be related to diminished expression of the beta 1 integrin subunit and perhaps to impaired proliferation.
Sponsel
H T
HT
Department of Medicine, Denver Veterans Affairs Medical Center, Colorado, USA.
Alfrey
A C
AC
Hammond
W S
WS
Durr
J A
JA
Ray
C
C
Anderson
R J
RJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005290:Ferric Compounds / Q000633:toxicity; D019012:Integrin beta1 / Q000378:metabolism; D007501:Iron / Q000378:metabolism / Q000633:toxicity*; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018374:LLC-PK1 Cells; D008854:Microscopy, Electron; D013552:Swine; D014945:Wound Healing / Q000187:drug effects
D005290:Ferric Compounds; D019012:Integrin beta1; C025314:ferric citrate; D007501:Iron; D000262:Adenylyl Cyclases