Abstract
Background:
Congenital disorders of glycosylation (CDG) patients share a basic feature of protein hypoglycosylation. Activity of growth factors and their receptors, glycoproteins playing a pivotal role during child development, remains unexplored in CDG patients.
Methods:
Peripheral blood lymphocytes (PBL) isolated from 9 CDG patients and 12 healthy controls were cultured in the presence of fetal bovine serum (FBS), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1), and BrdU incorporation was measured. Levels of plasma IGF-1 and PBL IGF-1 receptor (IGF-1R) and its glycosylation were detected using immunoassay and western blot.
Results:
CDG patients showed significantly less (P < 0.01) serum-induced 5′-Bromo-2′-deoxyuridine (BrdU) incorporation in PBL than in controls. PDGF-/FGF-stimulated BrdU incorporation showed no difference in patients and controls, whereas IGF-1-induced DNA synthesis was significantly (P < 0.01) less in patients. Plasma IGF-1 levels and PBL IGF-1 receptor protein were significantly (P < 0.01) reduced in patients as compared to controls. IGF-1 receptor in PBL of all CDG patients had significantly (P < 0.01) reduced carbohydrate content when compared with control.
Conclusions:
These results show selective impairment of IGF-1-induced DNA synthesis in lymphocytes of CDG patients through decreased gene expression and hypoglycosylation of the IGF-1 receptor.
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Technical assistance of Nini Mathew is greatly acknowledged.
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Dhaunsi, G. Receptor-mediated selective impairment of insulin-like growth factor-1 activity in congenital disorders of glycosylation patients. Pediatr Res 81, 526–530 (2017). https://doi.org/10.1038/pr.2016.96
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DOI: https://doi.org/10.1038/pr.2016.96
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