Abstract: PO1722
Podocyte-Specific Extracellular Vesicles Yield Novel Insight into Intercellular Signaling in the Glomerulus
Session Information
- Podocyte Pathobiology: Basic Science Studies and Animal Models
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Pape, Annika, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Teicher, Kilian, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Homeyer, Inka Christina, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Deheshwar, Kian, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Obser, Anja, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Oberüber, Valerie Thalia, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Wanner, Nicola, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Meyer-Schwesinger, Catherine, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Huber, Tobias B., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
- Braun, Fabian, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
Background
Extracellular vesicles (EVs) have been identified to play an essential role in basic pathological processes such as priming of the metastatic niche, autoimmunity and propagation of insulin resistance. Nevertheless, knowledge about their role in kidney health and disease remains scarce. A new group of EVs, shed upon apoptosis with the ability to induce a proliferative effect in neighboring cells, was recently identified in cell culture models as well as experimental glomerulonephritis. This study aimed to characterize these medium-sized EVs and the signaling propagated by them in podocyte damage.
Methods
Using differential centrifugation and filtration we established a protocol to separate medium-sized EVs from cell culture supernatants, kidney tissue and urine samples. With Western Blot, immunofluorescence microscopy and image flow cytometry we investigated the release dynamics of podocyte-specific vesicles in different models of murine podocyte damage in vitro and in vivo. Furthermore, cross culture experiments and life microscopy were used to determine the effect of podocyte-specific medium-sized EVs on parietal epithelial cells.
Results
Podocyte-specific medium-sized EVs were detected in baseline podocyte culture supernatant, untreated murine kidney tissue as well as the urine of healthy human volunteers. Vesicle quantification revealed a drastic increase of vesicle release upon podocyte damage both in vitro and in vivo. Interestingly, podocyte-specific EVs exerted different effects on the proliferative and migratory behavior of primary parietal epithelial cells.
Conclusion
Our study represents the first investigation of podocyte-specific medium-sized extracellular vesicles, their release dynamics and functional implications in health and disease. Ongoing analyses aim to characterize their proteomic content and effect other renal epithelial cells. As these vesicles can be separated without advanced equipment such as ultracentrifuges, we believe they could also be a valuable source for biomarker research in various nephropathies.