Subtotal ablation of parietal epithelial cells induces crescent formation

• Verfasst von: Sicking, Eva-Maria [VerfasserIn]
• Verfasst von: Kriz, Wilhelm [VerfasserIn]
• Titel: Subtotal ablation of parietal epithelial cells induces crescent formation
• Verf.angabe: Eva-Maria Sicking, Astrid Fuss, Sandra Uhlig, Peggy Jirak, Henry Dijkman, Jack Wetzels, Daniel R. Engel, Torsten Urzynicok, Stefan Heidenreich, Wilhelm Kriz, Christian Kurts, Tammo Ostendorf, Jürgen Floege, Bart Smeets, and Marcus J. Moeller
• Jahr: 2012
• Umfang: 12 S.
• Fussnoten: Published online: November 24, 2011 ; Gesehen am 10.08.2018
• Titel Quelle: Enthalten in: American Society of NephrologyJournal of the American Society of Nephrology
• Ort Quelle: Washington, DC : American Society of Nephrology, 1990
• Jahr Quelle: 2012
• Band/Heft Quelle: 23(2012), 4, Seite 629-640
• ISSN Quelle: 1533-3450
• DOI: doi:10.1681/ASN.2011050449
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1578466075

Abstract

Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established an inducible transgenic mouse to allow subtotal ablation of PECs. Proteinuria developed during doxycycline-induced cellular ablation but fully reversed 26 days after termination of doxycycline administration. The ablation of PECs was focal, with only 30% of glomeruli exhibiting histologic changes; however, the number of PECs was reduced up to 90% within affected glomeruli. Ultrastructural analysis revealed disruption of PEC plasma membranes with cytoplasm shedding into Bowman’s space. Podocytes showed focal foot process effacement, which was the most likely cause for transient proteinuria. After >9 days of cellular ablation, the remaining PECs formed cellular extensions to cover the denuded Bowman’s capsule and expressed the activation marker CD44 de novo. The induced proliferation of PECs persisted throughout the observation period, resulting in the formation of typical cellular crescents with periglomerular infiltrate, albeit without accompanying proteinuria. In summary, subtotal ablation of PECs leads the remaining PECs to react with cellular activation and proliferation, which ultimately forms cellular crescents.