Mesangial cell hyperplasia is a feature common to several human glomerular diseases. The cause of this increased cell number is unknown. The authors assessed mesangial cells in vitro and found that they possessed an insulinlike growth factor-1 (IGF-1) receptor consisting of α and β units (Mr, 130 k and 90 k respectively). Fifty percent inhibition of IGF-1 specific binding to the receptor required 1 x 10-9 M IGF-1, > 1 x 10-6 M insulin and 1 x 10-7 M multiplication stimulating activity (MSA). Analysis of binding by the method of Scatchard revealed one type of IGF-1 receptor with a Kd of 1.35 x 10-9 M, and a number per cell of 1.04 x 105. Binding studies on whole glomeruli had similar specificity and there were 7.17 x 107 receptors per glomerulus (Kd, 1.12 x 10-9 M). Examination of the effect of IGF-1 on the cell cycle revealed the exposure of cells to both IGF-1 and platelet-derived growth factor (PDGF) led to a significant increase in 3H-thymidine incorporation into cell layers. Antibody to PDGF abolished only that response due to PDGF. Similarly the labeling index of cells pretreated with PDGF, washed, and then exposed to IGF-1 was increased, whereas if the order of ligand exposure was reversed, there was no such additive effect. Finally, PDGF increased RNA and protein synthesis, and this response was not enhanced by IGF-1. In summary, human mesangial cells and whole glomeruli possess IGF-1-specific receptors and IGF-1 was found to act as a progression factor in the cell cycle.
|Number of pages
|American Journal of Pathology
|Published - 1989
ASJC Scopus subject areas
- Pathology and Forensic Medicine