Abstract
Children with chronic renal failure (CRF) have normal or high serum levels of GH, IGF-I, and IGF-II. Despite this, the serum of CRF patients has low IGF bioactivity, which may contribute to CRF growth failure. Recent studies suggest that excess IGF binding proteins (IGFBPs) in the ≈35-kD fractions of CRF serum contribute to this low IGF bioactivity. This report characterizes a 29-kD form of IGFBP-3, IGFBP-329, which accumulates in the ≈35-kD fractions of CRF serum and peritoneal dialysate. Deglycosylation and[125I]IGF ligand blot studies show that IGFBP-329 is a glycosylated IGFBP-3 fragment with low affinity for IGF peptides. Using an IGFBP-3 antibody column, IGFBP-329 was purified to homogeneity from the≈35-kD fractions of peritoneal dialysate from children with CRF. Compared with native IGFBP-3, pure IGFBP-329 has a 4-10-fold lower affinity for IGF-II and a 200-fold lower affinity for IGF-I. Consistent with the binding data, IGFBP-329 inhibited IGF-II-stimulated thymidine incorporation in chondrosarcoma cells, but was a less potent inhibitor than native IGFBP-3; also, native IGFBP-3 clearly inhibited IGF-I-stimulated thymidine incorporation in chondrosarcoma cells and potentiated IGF-I-stimulated aminoisobutyric acid uptake in bovine fibroblasts, but higher concentrations of IGFBP-329 had no effect on these IGF-I actions. Thus, the 29-kD IGFBP-3 form that accumulates in CRF serum and extravascular spaces is an IGFBP-3 fragment that may modulate IGF-II, but not IGF-I, effects on target tissues. Whether IGFBP-329 plays any role in the growth failure of children with CRF remains to be determined.
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Abbreviations
- CRF:
-
chronic renal failure
- IGFBP:
-
insulin-like growth factor binding protein
- PD:
-
peritoneal dialysate
- Endo-F:
-
endoglycosidase F
- DMEM:
-
Dulbecco's modified Eagle's medium
- AIB:
-
aminoisobutyric acid
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Acknowledgements
The authors thank Laurie K. Bale for expert technical assistance.
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Supported by National Institutes of Health Grant RO1 DK-38773 (to D.R.P.).
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Durham, S., Mohan, S., Liu, F. et al. Bioactivity of a 29-Kilodalton Insulin-Like Growth Factor Binding Protein-3 Fragment Present in Excess in Chronic Renal Failure Serum. Pediatr Res 42, 335–341 (1997). https://doi.org/10.1203/00006450-199709000-00014
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DOI: https://doi.org/10.1203/00006450-199709000-00014
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