Growth factor binding and bioactivity in human kidney epithelial cell cultures |
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Authors: | Ted Gansler Wei-Chao Hsu T Stokes Gramling Katherine A Robinson Maria G Buse Ned Blocker Linda Roy Sadie Green A Julian Garvin Donald A Sens |
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Institution: | (1) Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 171 Ashley Avenue, 29425 Charleston, South Carolina;(2) Department of Medicine, Medical University of South Carolina, 171 Ashley Avenue, 29425 Charleston, South Carolina;(3) Department of Neurology, Medical University of South Carolina, 171 Ashley Avenue, 29425 Charleston, South Carolina |
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Abstract: | Summary Insulinlike growth factors (IGF) and epidermal growth factor (EGF) are produced in renal tissue, as are specific receptors
for these hormones. To evaluate the significance of these observations to regulation of renal tubular cell proliferation,
we have examined the interaction of IGF and EGF with cultured human proximal tubular epithelial cells (HPT). HPT cells showed
specific binding of IGF-1, insulin, and EGF. IGF-1 binding was inhibited by antibody to the type 1 IGF receptor (α-IR3). Insulin
receptors and type 1 IGF receptors were identified by bifunctional cross-linking. IGF-1, insulin, and EGF stimulated 3H]thymidine incorporation by 77, 73, and 87%, respectively. Haft maximal stimulation by IGF-1, insulin, and EGF was produced
with 4×10−9
M, 2.5×10−8
M, and 8×10−10
M concentrations of these hormones. α-IR3 inhibited stimulation of thymidine incorporation by IGF-1 and insulin but had no
effect in EGF-stimulated thymidine incorporation. EGF and high concentrations of insulin both stimulated cell proliferation
by 83 and 79%, respectively. These data are consistent with regulation of tubular epithelial proliferation by IGF-1, insulin,
and EGF and suggest that the mitogenic activity of both insulin and IGF-1 is mediated by the type 1 IGF receptor.
Supported by grants CA37887 and DK32889 from the National Institutes of Health, Bethesda, MD, and by a Medical University
of South Carolina institutional grant. |
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Keywords: | kidney cell culture insulinlike growth factors epidermal growth factor |
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