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Stimulation of the calcium-sensing receptor stabilizes the podocyte cytoskeleton, improves cell survival, and reduces toxin-induced glomerulosclerosis

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Calcimimetics increase the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium for efficient control of hyperparathyroidism. Recent studies suggest that there are beneficial effects of calcimimetics beyond the control of bone and mineral homeostasis. Here, we tested whet...

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Main Authors: Oh, Jun (Author) , Schröder, Julia Cornelia (Author) , Bloch, Jacek (Author) , Hettgen, Verena (Author) , Müller, Julian (Author) , Li, Li (Author) , Hoemme, Meike (Author) , Groß-Weissmann, Marie-Luise (Author) , Penzel, Roland (Author) , Mundel, Peter (Author) , Schaefer, Franz (Author) , Schmitt, Claus P. (Author)
Format: Article (Journal)
Language:English
Published: 20 April 2011
In: Kidney international
Year: 2011, Volume: 80, Issue: 5, Pages: 483-492
ISSN:1523-1755
DOI:10.1038/ki.2011.105
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ki.2011.105
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0085253815550655
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Author Notes:Jun Oh, Julia Beckmann, Jacek Bloch, Verena Hettgen, Julian Mueller, Li Li, Meike Hoemme, Marie-Luise Gross, Roland Penzel, Peter Mundel, Franz Schaefer and Claus P. Schmitt
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Summary:Calcimimetics increase the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium for efficient control of hyperparathyroidism. Recent studies suggest that there are beneficial effects of calcimimetics beyond the control of bone and mineral homeostasis. Here, we tested whether the calcium-sensing receptor is also expressed and functionally relevant in podocytes. Analysis of microarray data using Gene Set Enrichment Analysis found that the calcimimetic R-568 influenced various pathways related to oxidative stress, cytoskeletal regulation, cell proliferation, and survival in cultured podocytes. R-568 induced a dose- and time-dependent phosphorylation of the ERK1/2-P90RSK-CREB signaling cascade, and induced pro-survival phosphorylation of BAD and Bcl-xl, thus reducing puromycin aminonucleoside (PAN)-induced podocyte apoptosis by half. Moreover, R-568 preserved the actin cytoskeleton in podocytes exposed to PAN and improved recovery from exposure to cytochalasin D, a reversible inhibitor of actin polymerization. In rats, co-administration of R-568 prevented the proteinuria caused by a single dose of PAN and attenuated the glomerulosclerosis and loss of GFR caused by repetitive puromycin treatment. Hence, calcimimetics limit podocyte damage by antiapoptotic and cytoskeleton-stabilizing effects and may constitute a new approach in the prevention and treatment of glomerular disease.
Item Description:Gesehen am 12.10.2022
Physical Description:Online Resource
ISSN:1523-1755
DOI:10.1038/ki.2011.105

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