Abstract: TH-PO753
The Influence of Normal and Preeclamptic Syncytiotrophoblast Extracellular Vesicles on Human Podocytes
Session Information
- Sex and Reproductive Factors in Kidney Health
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Women's Health and Kidney Diseases
- 2100 Women's Health and Kidney Diseases
Authors
- Jiang, Shuhan, University of Oxford, Oxford, Oxfordshire, United Kingdom
- Awoyemi, Toluwalase, University of Oxford, Oxford, Oxfordshire, United Kingdom
- Rahbar, Maryam, University of Oxford, Oxford, Oxfordshire, United Kingdom
- Logenthiran, Prassana Varun, University of Oxford, Oxford, Oxfordshire, United Kingdom
- Zhang, Wei, University of Oxford, Oxford, Oxfordshire, United Kingdom
- Tuffin, Jack P., University of Bristol, Bristol, Bristol, United Kingdom
- Saleem, Moin, University of Bristol, Bristol, Bristol, United Kingdom
- Vatish, Manu, University of Oxford, Oxford, Oxfordshire, United Kingdom
Background
Circulating levels of syncytiotrophoblast extracellular vesicles (STBEVs) increase throughout gestation in normal pregnant (NP) women, and their levels are higher in preeclampsia (PE). In NP, glomerular filtration rates (GFR) increase by 50%, while in PE GFR can reduce by up to 32% which implicates the impaired glomerular filtration barrier (GFB) function. Podocytes are specialised renal cells which are involved in GFB maintenance. We aimed to evaluate whether small STBEVs (sSTBEVs) from NP and PE can be internalized by podocytes and influence function.
Methods
NP (n=3) and PE (n = 3) sSTBEVs were isolated by dual-lobe placental perfusion and differential centrifugation. sSTBEVs were phenotyped by immunoblotting, nanoparticle tracking analysis and transmission electron microscopy. sSTBEVs internalization by podocytes was assessed by flow cytometry and confocal microscopy. qPCR was used to analyze if sSTBEVs could transfer placental specific C19 miRNA into podocytes. Podocyte nephrin expression, migration ability, actin cytoskeleton and adhesion ability were assessed after treatment with sSTBEVs.
Results
The internalization of sSTBEVs by podocytes could be observed from 30mins and was time and dose dependent. There was no significant difference in number of sSTBEVs from NP and PE internalised by podocytes. We were able to detect placental specific C19 miRNA in podocytes treated with these sSTBEVs. Podocyte nephrin expression was increased by 1.9-fold (p<0.05) and podocyte migration ability was upregulated by 1.2-fold (p<0.05). F-actin staining was enhanced across the podocytes after NP sSTBEVs treatment (p<0.05). In contrast, PE sSTBEVs treatment showed no change in nephrin expression or podocyte migration ability. Additionally, podocyte adhesion ability was impaired and F-actin appeared stressed (cortical ring formation).
Conclusion
NP and PE sSTBEVs can be taken up by podocytes. NP sSTBEVs enhanced podocyte function via elevated nephrin expression and migration ability. In contrast, PE sSTBEVs impaired podocyte via reduced adhesion ability and nephrin expression was unchanged. We speculate the enhanced functions of podocytes after NP sSTBEVs treatment may contribute GFB maintenance while sSTBEVs from PE may contribute to GFB damage.