title: Subtotal ablation of parietal epithelial cells induces crescent formation.
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.
authors.affiliation: Division of Nephrology and Clinical Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Sicking
authors.forename: Astrid
authors.initials: A
authors.lastname: Fuss
authors.forename: Sandra
authors.initials: S
authors.lastname: Uhlig
authors.forename: Peggy
authors.initials: P
authors.lastname: Jirak
authors.forename: Henry
authors.initials: H
authors.lastname: Dijkman
authors.forename: Jack
authors.initials: J
authors.lastname: Wetzels
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Engel
authors.forename: Torsten
authors.initials: T
authors.lastname: Urzynicok
authors.forename: Stefan
authors.initials: S
authors.lastname: Heidenreich
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Kriz
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Bart
authors.initials: B
authors.lastname: Smeets
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Moeller
mesh_terms: D000818:Animals; D050476:Bowman Capsule / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004318:Doxycycline; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology* / Q000601:surgery*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000473:pathology* / Q000601:surgery*; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D011507:Proteinuria / Q000139:chemically induced; D011897:Random Allocation
chemical_list: D004318:Doxycycline