Increased Insulin-like Growth Factor Binding Protein-1 Phosphorylation in Decidualized Stromal Mesenchymal Cells in Human Intrauterine Growth Restriction Placentas.

Abstract

Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each). We performed dual immunofluorescence immunohistochemistry (IHC) using IGFBP-1 and vimentin as decidual and mesenchymal markers, respectively. Employing a unique strategy with imaging software, we extracted signal intensity of IGFBP-1 expressed specifically from truly decidualized cells of the placenta. Relative IGFBP-1 was increased (85%; p=0.0001) and using custom phospho-site-specific antibodies, we found that IGFBP-1 phosphorylation (pSer101; +40%, p=0.0677/pSer119; +60%, p=0.0064/pSer169; +100%, p=0.0021) was markedly enhanced in IUGR. Together, our data links for the first time, increased decidual IGFBP-1 phosphorylation at discrete sites with human IUGR. These novel findings suggest that hyperphosphorylation of IGFBP-1 in decidualized stromal mesenchymal decidua basalis contributes to potentially elevated levels of phosphorylated IGFBP-1 in maternal circulation in IUGR pregnancies.

• Authors: Sahil S Singal, Karen Nygard, Robert Gratton, Thomas Jansson, Madhulika B Gupta
• Journal: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society (J Histochem Cytochem) Vol. 66 Issue 9 Pg. 617-630 (09 2018) ISSN: 1551-5044 [Electronic] United States
• PMID: 29718759 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• IGFBP1 protein, human
• Insulin-Like Growth Factor Binding Protein 1

Topics

• Adult
• Decidua (pathology)
• Female
• Fetal Growth Retardation (pathology)
• Fluorescent Antibody Technique (methods)
• Humans
• Insulin-Like Growth Factor Binding Protein 1 (analysis)
• Mesenchymal Stem Cells (pathology)
• Microscopy, Fluorescence
• Phosphorylation
• Pregnancy