Insulin-like growth factor-I receptor and binding proteins in rat kidney after nephron loss.

Abstract

Insulin-like growth factor (IGF)-binding proteins and the IGF-I receptor in rat kidney were studied to gain perspective on their potential roles in the control of renal cell mass. Thirty days after nephrectomy (UNx), membranous whole-kidney binding of IGF-I averaged 9.5 +/- 1.0 pmol/kidney, whereas binding to sham-operated controls (SNx) averaged 6.3 +/- 0.8 pmol/kidney (N = 6; P < 0.01). Scatchard analysis of IGF-I binding per milligram of protein to glomerular membranes or proximal tubule basolateral membranes (BLM) at Day 30 did not reveal significance differences in Bmax or KD between SNx and UNx; however, protein per glomerulus increased from 361 +/- 33 ng/glomerulus in SNx animals to 826 +/- 123 ng/glomerulus in UNx rats (N = 6; P < 0.002). Histomorphometrics documented an increase in proximal tubule circumference per cell and an increase in the basolateral/basement membrane ratio. IGF-I affinity labeling studies demonstrated three proteins in both glomerular membranes and proximal tubule BLM; molecular weight approximately 140,000 d, the alpha subunit of the IGF-I receptor, a protein > 200,000 d, and a protein approximately 31,000 d that was immunostained with IGF-binding protein-5 antibodies. Differences in expression between SNx and UNx were not observed at Day 30 in either glomeruli or BLM. These studies suggest that cytosolic hypertrophy of proximal nephron structures is accompanied by membrane hypertrophy with a fixed density of IGF-I receptor and IGF-binding protein-5.