Abstract: TH-OR045
Senescence as an Underlying Mechanism of Podocyte Injury in Preeclampsia
Session Information
- Glomerular Precision Nephrology: Novel Mechanisms, Biomarkers, and Therapeutic Targets
November 06, 2025 | Location: Room 310A, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Women's Health and Kidney Diseases
- 2200 Women's Health and Kidney Diseases
Authors
- Suvakov, Sonja, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Hatamova, Jennet, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Gavrilovici, Paul, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Dokic, Vladimir, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Garovic, Vesna D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Preeclampsia (PE) is a pregnancy-specific condition characterized by hypertension accompanied by kidney injury. In addition to proteinuria, which is common in PE, there is significant podocyte loss. However, mechanisms underlying podocyte injury in PE have been poorly investigated. As we have previously reported, the presence of cellular senescence in the kidneys of women with PE, we explored whether cellular senescence could represent a mechanism of podocyte injury in PE.
Methods
Human immortalized differentiated podocytes were treated for 48h with 20% human PE pooled serum and assessed for the presence of cellular senescence by senescence-associated (SA) beta galactosidase staining, SA gene expression and secretome. Podocyte injury was tested by a cell adhesion assay and measurement of extracellular vesicles (EVs) positive for podocin and nephrin. Podocyte function was tested with the wound scratch assay. Comparison was made to the podocytes treated with regular media (control group).
Results
Human pooled PE serum used to treat podocytes had higher concentrations of SA markers like MCP-1, GROa, IL1A, MIF, IGFBP2, TNFR2, and TNFa compared to the serum of normotensive pregnant women. When exposed to the PE serum, podocytes exhibit increased SA beta galactosidase staining vs. control group. This is accompanied by increased expression of several SA genes notably MCP1, IL6 and PAI1. No significant changes in p16 and p21 gene expressions were observed. In conditioned media, PE treated podocytes had higher concentrations of SA markers, TGF-β, IL-8 and IL-6, while VEGF was decreased. There was significant PE-treated podocyte detachment compared to the control group (13% vs. 4%). Secretion of nephrin- and podocin-positive EVs, another indicator of podocyte injury, was higher in the conditioned media of PE treated podocytes compared to controls. Podocytes treated with PE serum exhibited functional impairment as observed by the wound scratch assay. Namely, the wound area of the PE injured podocytes was significantly higher after 24h compared to controls.
Conclusion
Cellular senescence is present in podocytes treated with PE serum. These podocytes exhibit molecular and functional signs of injury consistent with senescence, which can be one of the contributing mechanisms leading to podocyte injury and loss in PE.