Growth factor binding and bioactivity in human kidney epithelial cell cultures

Area of Science:

• Nephrology
• Cell Biology
• Endocrinology

Background:

• Renal tissue produces insulinlike growth factors (IGF) and epidermal growth factor (EGF).
• Specific receptors for these hormones are present in kidney tissue.
• The role of IGF and EGF in regulating renal tubular cell proliferation requires further investigation.

Purpose of the Study:

• To investigate the interaction of IGF and EGF with cultured human proximal tubular epithelial cells (HPT).
• To determine the significance of these interactions in regulating renal tubular cell proliferation.

Main Methods:

• HPT cells were cultured and exposed to IGF-1, insulin, and EGF.
• Specific binding of hormones to HPT cells was assessed.
• Type 1 IGF receptors and insulin receptors were identified using bifunctional cross-linking.
• The effect of IGF-1, insulin, and EGF on [3H]thymidine incorporation was measured.
• The impact of an antibody to the type 1 IGF receptor (alpha-IR3) on hormone-stimulated proliferation was evaluated.

Main Results:

• HPT cells exhibited specific binding for IGF-1, insulin, and EGF.
• IGF-1 binding was inhibited by alpha-IR3 antibody.
• IGF-1, insulin, and EGF significantly stimulated [3H]thymidine incorporation.
• Half-maximal stimulation occurred at specific hormone concentrations (IGF-1: 4x10^-9 M, insulin: 2.5x10^-8 M, EGF: 8x10^-10 M).
• Alpha-IR3 inhibited IGF-1 and insulin-stimulated thymidine incorporation but not EGF-stimulated incorporation.
• EGF and high insulin concentrations stimulated cell proliferation.

Conclusions:

• IGF-1, insulin, and EGF play a role in regulating renal tubular epithelial cell proliferation.
• The mitogenic activity of both insulin and IGF-1 appears to be mediated through the type 1 IGF receptor.