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Publication : Subtotal ablation of parietal epithelial cells induces crescent formation.

First Author  Sicking EM Year  2012
Journal  J Am Soc Nephrol Volume  23
Issue  4 Pages  629-40
PubMed ID  22282596 Mgi Jnum  J:294785
Mgi Id  MGI:6451339 Doi  10.1681/ASN.2011050449
Citation  Sicking EM, et al. (2012) Subtotal ablation of parietal epithelial cells induces crescent formation. J Am Soc Nephrol 23(4):629-40
abstractText  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.
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