1. Growth factor binding and bioactivity in human kidney epithelial cell cultures.
- Author
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Gansler T, Hsu WC, Gramling TS, Robinson KA, Buse MG, Blocker N, Roy L, Green S, Garvin AJ, and Sens DA
- Subjects
- Cells, Cultured, DNA biosynthesis, Epidermal Growth Factor metabolism, Epidermal Growth Factor pharmacology, Humans, Insulin metabolism, Insulin pharmacology, Insulin-Like Growth Factor I pharmacology, Kidney Tubules, Proximal cytology, Receptors, Somatomedin, Thymidine metabolism, ErbB Receptors metabolism, Insulin-Like Growth Factor I metabolism, Kidney Tubules, Proximal metabolism, Receptor, Insulin metabolism, Receptors, Cell Surface metabolism, Somatomedins metabolism
- Abstract
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 (alpha-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. Half maximal stimulation by IGF-1, insulin, and EGF were produced with 4 X 10(-9) M, 2.5 X 10(-8) M, and 8 X 10(-10) M concentrations of these hormones. Alpha-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.
- Published
- 1990
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