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Parietal epithelial cells maintain the epithelial cell continuum forming Bowman’s space in focal segmental glomerulosclerosis

Laura Miesen, Péter Bándi, Brigith Willemsen, Fieke Mooren, Thiago Strieder, Eva Boldrini, Vedran Drenic, Jennifer Eymael, Roy Wetzels, Johannes Lotz, Nick Weiss, Eric Steenbergen, Toin H. van Kuppevelt, Merijn van Erp, Jeroen van der Laak, Nicole Endlich, Marcus J. Moeller, Jack F.M. Wetzels, Jitske Jansen, Bart Smeets*

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated parietal epithelial cells (PECs) invading the glomerular tuft. The segmental scars interrupt the epithelial continuum. However, non-sclerotic segments seem to be preserved even in glomeruli with advanced lesions. We studied the histology of the segmental pattern in Munich Wistar Frömter rats, a model for secondary FSGS. Our results showed that matrix layers lined with PECs cover the sclerotic lesions. These PECs formed contacts with podocytes of the uninvolved tuft segments, restoring the epithelial continuum. Formed Bowman's spaces were still connected to the tubular system. In biopsies of patients with secondary FSGS, we also detected matrix layers formed by PECs, separating the uninvolved from the sclerotic glomerular segments. PECs have a major role in the formation of glomerulosclerosis; we show here that in FSGS they also restore the glomerular epithelial cell continuum that surrounds Bowman's space. This process may be beneficial and indispensable for glomerular filtration in the uninvolved segments of sclerotic glomeruli.
OriginalspracheEnglisch
Aufsatznummerdmm046342
ZeitschriftDMM Disease Models and Mechanisms
Jahrgang15
Ausgabenummer3
ISSN1754-8403
DOIs
PublikationsstatusVeröffentlicht - 03.2022

Fördermittel

The study was funded by Nierstichting (Dutch Kidney Foundation; grant 14A3D104) and Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organization for Scientific Research; NWO VIDI grant 016.156.363). The authors wish to thank Lars Damen and Arie Oosterhof (Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands) for their contribution in the production and delivery of LKIV69, and Muradije Demirel-Andishmand (Department of Pathology, Radboud University Medical Center) for cutting consecutive sections of the embedded MWF rat tissue for us. The study was funded by Nierstichting (Dutch Kidney Foundation; grant 14A3D104) and Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organization for Scientific Research; NWO VIDI grant 016.156.363).

TrägerTrägernummer
Department of Biochemistry
Department of Pathology
Lars Damen and Arie Oosterhof
Muradije Demirel-Andishmand
Radboud Institute for Molecular Life Sciences
Nierstichting14A3D104
Nederlandse Organisatie voor Wetenschappelijk Onderzoek016.156.363
Radboud Universitair Medisch Centrum

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