Hexosamine pathway regulates StarD7 expression in JEG-3 cells.

Area of Science:

• Cell Biology
• Metabolic Pathways
• Trophoblast Biology

Background:

• StarD7 is a lipid-binding protein crucial for mitochondrial phosphatidylcholine delivery.
• Wnt/β-catenin signaling activates the StarD7 promoter.
• The hexosamine biosynthetic pathway (HBP) is implicated in β-catenin regulation.

Purpose of the Study:

• To investigate if glucose levels modulate StarD7 expression through HBP in trophoblast cells.
• To explore the relationship between glucose metabolism, HBP, and unfolded protein response (UPR) in trophoblast cells.

Main Methods:

• JEG-3 trophoblast cells were treated with varying glucose concentrations (25 mM) and HBP inhibitors.
• Expression levels of StarD7, β-catenin, and UPR markers (GRP78, Ire1α, calnexin, p-eIF2α, total eIF2α, XBP1 mRNA) were measured.

Main Results:

• High glucose increased StarD7 and β-catenin expression, effects abolished by HBP inhibitors.
• Decreased glucose reduced StarD7 and increased UPR markers (GRP78, Ire1α).
• High glucose correlated with high StarD7 and low GRP78, phospho-eIF2α, and XBP1 splicing, while Ire1α remained elevated.

Conclusions:

• Glucose modulates StarD7 and β-catenin expression in trophoblast cells via the HBP.
• A link exists between UPR and HBP in trophoblast cells, influenced by glucose availability.
• This study is the first to report glucose effects on StarD7 in trophoblast cells, highlighting StarD7's potential role in placental disorders.