Triiodothyronine enhances renal tubule cell replication by stimulating EGF receptor gene expression.
Thyroid hormone is known to accelerate renal function recovery following toxic acute renal failure. Because epidermal growth factor (EGF)-receptor activation is most likely critical in renal replicative repair, these studies were undertaken to assess whether triiodothyronine (T3), the most active form of thyroid hormone, may modulate EGF-induced renal proximal tubule cell proliferation by an effect on the EGF receptor. Rabbit renal proximal tubular cells were grown in primary culture and treated with or without T3 (0.1 or 1.0 nM) for 24 to 48 h. Compared with nontreated controls, T3 exposure led to significant increases in EGF-promoted DNA synthesis, as measured by [3H]thymidine incorporation, in renal tubule cells. Furthermore, T3 treatment resulted in increases in EGF receptor mRNA in proximal tubule cells compared with nontreated cells and was associated with elevated numbers of EGF receptors on the cell surface of proximal tubule cells. EGF binding studies demonstrated that T3 treatment had only modest effects on Kd values of both the high-affinity binding site (0.19 nM) and the low-affinity binding site (3.7 nM) but substantially increased the maximal number of high-affinity sites from 3.8 x 10(3) to 9.4 x 10(3) receptors/cell and the maximal number of low-affinity sites from 132 x 10(3) to 199 x 10(3) receptors/cell. These findings suggest that a T3 effect to increase EGF receptor gene expression with resulting increases in the number of cell surface EGF receptors on renal proximal tubule cells and a potentiated mitogenic response to EGF may be a mechanism for thyroid hormone to enhance renal function recovery following toxic acute renal failure.
Humes
H D
HD
Department of Internal Medicine, Veterans Affairs Medical Center, Ann Arbor, Michigan.
Cieslinski
D A
DA
Johnson
L B
LB
Sanchez
I O
IO
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D012333:RNA, Messenger; D014284:Triiodothyronine; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors