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Bitte verwenden Sie diesen Link, wenn Sie dieses Dokument zitieren oder verlinken wollen: https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-62532

The ShGlomAssay Combines High-Throughput Drug Screening With Downstream Analyses and Reveals the Protective Role of Vitamin D3 and Calcipotriol on Podocytes

  • Chronic kidney disease (CKD) is a major public health burden affecting more than 500 million people worldwide. Podocytopathies are the main cause for the majority of CKD cases due to pathogenic morphological as well as molecular biological alterations of postmitotic podocytes. Podocyte de-differentiation is associated with foot process effacement subsequently leading to proteinuria. Since currently no curative drugs are available, high throughput screening methods using a small number of animals are a promising and essential tool to identify potential drugs against CKD in the near future. Our study presents the implementation of the already established mouse GlomAssay as a semi-automated high-throughput screening method—shGlomAssay—allowing the analysis of several hundreds of FDA-verified compounds in combination with downstream pathway analysis like transcriptomic and proteomic analyses from the same samples, using a small number of animals. In an initial prescreening we have identified vitamin D3 and its analog calcipotriol to be protective on podocytes. Furthermore, by using RT-qPCR, Western blot, and RNA sequencing, we found that mRNA and protein expression of nephrin, the vitamin D receptor and specific podocyte markers were significantly up-regulated due to vitamin D3- and calcipotriol-treatment. In contrast, kidney injury markers were significantly down-regulated. Additionally, we found that vitamin D3 and calcipotriol have had neither influence on the expression of the miR-21 and miR-30a nor on miR-125a/b, a miRNA described to regulate the vitamin D receptor. In summary, we advanced the established mouse GlomAssay to a semi-automated high-throughput assay and combined it with downstream analysis techniques by using only a minimum number of animals. Hereby, we identified the vitamin D signaling pathway as podocyte protective and to be counteracting their de-differentiation.

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Metadaten
Author: Marie-Christin Ristov, Tim Lange, Nadine Artelt, Neetika Nath, Andreas W. Kuss, Jochen Gehrig, Maja Lindenmeyer, Clemens D. Cohen, Sheraz Gul, Karlhans Endlich, Uwe Völker, Nicole Endlich
URN:urn:nbn:de:gbv:9-opus-62532
DOI:https://doi.org/10.3389/fcell.2022.838086
ISSN:2296-634X
Parent Title (English):Frontiers in Cell and Developmental Biology
Publisher:Frontiers Media S.A.
Place of publication:Lausanne
Document Type:Article
Language:English
Date of first Publication:2022/05/16
Release Date:2022/11/15
Tag:CKD—chronic kidney disease; compound; differentiation; glomerulus; podocyte; screening; vitamin D3
GND Keyword:-
Volume:10
Article Number:838086
Page Number:11
Faculties:Universitätsmedizin / Institut für Anatomie und Zellbiologie
Collections:Artikel aus DFG-gefördertem Publikationsfonds
Licence (German):License LogoCreative Commons - Namensnennung