Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions

Journal article


Publication Details

Author(s): Kuppe C, Leuchtle K, Wagner A, Kabgani N, Saritas T, Puelles VG, Smeets B, Hakroush S, van der Vlag J, Boor P, Schiffer M, Gröne HJ, Fogo A, Floege J, Moeller MJ
Journal: Kidney International
Publication year: 2019
ISSN: 0085-2538


Abstract

Beside the classical flat parietal epithelial cells (PECs), we investigated proximal tubular epithelial-like cells, a neglected subgroup of PECs. These cells, termed cuboidal PECs, make up the most proximal part of the proximal tubule and may also line parts of Bowman's capsule. Additionally, a third intermediate PEC subgroup was identified at the junction between the flat and cuboidal PEC subgroups at the tubular orifice. The transgenic mouse line PEC-rtTA labeled all three PEC subgroups. Here we show that the inducible Pax8-rtTA mouse line specifically labeled only cuboidal and intermediate PECs, but not flat PECs. In aging Pax8-rtTA mice, cell fate mapping showed no evidence for significant transdifferentiation from flat PECs to cuboidal or intermediate PECs or vice versa. In murine glomerular disease models of crescentic glomerulonephritis, and focal segmental glomerulosclerosis (FSGS), intermediate PECs became more numerous. These intermediate PECs preferentially expressed activation markers CD44 and Ki-67, suggesting that this subgroup of PECs was activated more easily than the classical flat PECs. In mice with FSGS, cuboidal and intermediate PECs formed sclerotic lesions. In patients with FSGS, cells forming the tip lesions expressed markers of intermediate PECs. These novel PEC subgroups form sclerotic lesions and were more prone to cellular activation compared to the classical flat PECs in disease. Thus, colonization of Bowman's capsule by cuboidal PECs may predispose to lesion formation and chronic kidney disease. We propose that tip lesions originate from this novel subgroup of PECs in patients with FSGS.


FAU Authors / FAU Editors

Schiffer, Mario Prof. Dr. med.
Lehrstuhl für Innere Medizin IV


External institutions
Radboud university medical center / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Southern Medical University / 南方医科大学
Universitätsklinikum Göttingen
Vanderbilt University


How to cite

APA:
Kuppe, C., Leuchtle, K., Wagner, A., Kabgani, N., Saritas, T., Puelles, V.G.,... Moeller, M.J. (2019). Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions. Kidney International. https://dx.doi.org/10.1016/j.kint.2019.01.037

MLA:
Kuppe, Christoph, et al. "Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions." Kidney International (2019).

BibTeX: 

Last updated on 2019-14-05 at 08:08