Paediatrics Publications
Title
Exposure of decidualized HIESC to low oxygen tension and leucine deprivation results in increased IGFBP-1 phosphorylation and reduced IGF-I bioactivity
Document Type
Article
Publication Date
9-5-2017
Journal
Molecular and Cellular Endocrinology
Volume
452
First Page
1
Last Page
14
URL with Digital Object Identifier
10.1016/j.mce.2017.04.005
Abstract
Phosphorylation of decidual IGFBP-1 enhances binding of IGF-I, limiting the bioavailability of this growth factor which may contribute to reduced placental and fetal growth. The mechanisms regulating decidual IGFBP-1 phosphorylation are incompletely understood. Using decidualized human immortalized endometrial stromal cells we tested the hypothesis that low oxygen tension or reduced leucine availability, believed to be common in placental insufficiency, increase the phosphorylation of decidual IGFBP-1. Multiple reaction monitoring-MS (MRM-MS) was used to quantify IGFBP-1 phosphorylation. MRM-MS validated the novel phosphorylation of IGFBP-1 at Ser58, however this site was unaffected by low oxygen tension/leucine deprivation. In contrast, significantly elevated phosphorylation was detected for pSer119, pSer98/pSer101 and pSer169/pSer174 sites. Immunoblotting and dual-immunofluorescence using phosphosite-specific IGFBP-1 antibodies further demonstrated increased IGFBP-1 phosphorylation in HIESC under both treatments which concomitantly reduced IGF-I bioactivity. These data support the hypothesis that down regulation of IGF-I signaling links decidual IGFBP-1 hyperphosphorylation to restricted fetal growth in placental insufficiency.