Abstract: TH-PO784
Novel Parietal Epithelial Cell Subpopulations in FSGS and the Origin of the Glomerular Tip Lesion
Session Information
- Cellular Crosstalk in Glomerular Diseases - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Kuppe, Christoph, University Hospital of RWTH Aachen, Aachen, Germany
- Saritas, Turgay, University Hospital of RWTH Aachen, Aachen, Germany
- Puelles, Victor G., University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Smeets, Bart, Radboud University Medical Center, Nijmegen, Netherlands
- Boor, Peter, University Hospital of RWTH Aachen, Aachen, Germany
- Schiffer, Mario, Hannover Medical School, Hannover, Germany
- Fogo, Agnes B., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Groene, Hermann-Josef, German Cancer Research Center, Heidelberg, Germany
- Floege, Jürgen, RWTH University of Aachen, Aachen, Germany
- Moeller, Marcus J., University Hospital of RWTH Aachen, Aachen, Germany
Group or Team Name
- Moeller group
Background
Beside the classical flat PECs, proximal tubular epithelial like cells extend onto Bowman’s capsule (termed columnar PECs). In addition, a third intermediate PEC subgroup is identified at the junction between the flat and columnar PEC subgroups. Here, we have investigated the potential relevance of these PEC subgroups in focal segmental glomerulosclerosis (FSGS) for the first time.
Methods
The previously described transgenic mouse line PEC-rtTA labeled all three PEC subgroups. To allow lineage-tracing experiments, we identified the inducible Pax8-rtTA mouse line, which labeled specifically the two novel subgroups, columnar and intermediate PECs, but not flat PECs.
Results
In aging Pax8rtTA mice, cell fate mapping showed no evidence for significant transdifferentiation from flat PECs to columnar or intermediate PECs or vice versa. In glomerular disease (rapidly progressive glomerulonephritis, and FSGS), columnar PECs transitioned in part into the intermediate PEC phenotype. Intermediate PECs preferentially expressed activation markers CD44 and Ki-67, suggesting that this subgroup of PECs is activated more easily than the classical flat PECs. In murine FSGS, columnar and intermediate PECs formed sclerotic lesions contributing more than half of the cells. In FSGS patients, cells forming the tip lesions expressed markers of intermediate PECs.
Conclusion
In summary, columnar PECs acquire a transient phenotype termed intermediate PECs, which is more prone to cellular activation and proliferation compared to the classical flat PECs. Both novel PEC subgroups showed the capacity to form sclerotic lesions. We propose that in human FSGS patients tip lesions originate from this novel subgroup of PECs, which is located close to the tubular outlet.