Increased glucocerebrosidase expression and activity in preeclamptic placenta

Area of Science:

• Biochemistry
• Genetics
• Obstetrics

Background:

• Lysosomal glucosidase beta acid (GBA) deficiency is linked to Gaucher disease, Parkinsonism, and Lewy-body dementia.
• Increased GBA expression has not previously been associated with human disease.
• This study investigates GBA expression and activity in preeclamptic pregnancies.

Purpose of the Study:

• To determine GBA expression and activity levels in placental tissue from preeclamptic pregnancies.
• To identify novel GBA transcripts in the placenta.
• To explore potential correlations between GBA expression and other genes involved in placental function.

Main Methods:

• Quantitative PCR (qPCR) and GBA activity assays on 112 placental biopsies.
• Microarray analysis on 20 placental tissues.
• Cloning, expression, and analysis of alternatively spliced placental GBA transcripts in HEK293 cells.

Main Results:

• GBA is expressed in the syncytiotrophoblast layer of the human placenta from 5 weeks of gestation.
• Five novel, enzymatically inactive GBA transcripts were identified in the placenta.
• Both GBA RNA expression and enzymatic activity were found to be upregulated in preeclamptic placentas.
• GBA expression co-regulates with 158 genes, with enrichment analysis highlighting lysosomal function.
• GBA expression did not correlate with FLT1, a key preeclampsia marker, but negatively correlated with BMP4 and TFEB.

Conclusions:

• Hypothesize that increased GBA expression in preeclampsia may be linked to altered placentation via BMP4 signaling or vascularization through TFEB.
• Suggests ceramide, a product of GBA activity, as a potential link between increased GBA activity and preeclampsia.
• These pathways warrant further investigation for their role in preeclampsia.