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© 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

As the molecular mechanism of nephrotic syndrome remains largely undiscovered, patients continue to be exposed to the pros and cons of uniform glucocorticoid treatment. We explored whether the exposure of in vitro-cultivated podocytes to sera from children with steroid-sensitive or steroid-resistant nephrotic syndrome induces differences in gene expression profiles, which could help to elucidate the pathogenesis of the steroid response. Human immortalized podocytes were cultivated with patient sera for 3 days. After cell lysis, RNA extraction, 3′-mRNA libraries were prepared and sequenced. There were 34 significantly upregulated and 14 downregulated genes (fold difference <0.5 and >2.0, respectively, and false discovery rate-corrected p < 0.05) and 22 significantly upregulated and 6 downregulated pathways (false discovery rate-corrected p < 0.01) in the steroid-sensitive (n = 9) versus steroid-resistant group (n = 4). The observed pathways included upregulated redox reactions, DNA repair, mitosis, protein translation and downregulated cholesterol biosynthesis. Sera from children with nephrotic syndrome induce disease subtype-specific transcriptome changes in human podocytes in vitro. However, further exploration of a larger cohort is needed to verify whether clinically distinct types of nephrotic syndrome or disease activity may be differentiated by specific transcriptomic profiles and whether this information may help to elucidate the pathogenesis of the steroid response.

Details

Title
Nephrotic syndrome sera induce different transcriptomes in podocytes based on the steroid response
Author
Bezdicka, Martin 1   VIAFID ORCID Logo  ; Cinek, Ondrej 2   VIAFID ORCID Logo  ; Semjonov, Valerij 2 ; Polackova, Katerina 1 ; Sladkova, Eva 3 ; Zieg, Jakub 2   VIAFID ORCID Logo  ; Saleem, Moin A 4   VIAFID ORCID Logo  ; Soucek, Ondrej 1   VIAFID ORCID Logo 

 Vera Vavrova Lab/VIAL, Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic 
 Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic 
 Children's Clinic, Faculty of Medicine in Pilsen, University Hospital in Pilsen, Charles University, Pilsen, Czech Republic 
 Bristol Renal and Bristol Royal Hospital for Children, University of Bristol Medical School, Bristol, UK 
Section
ORIGINAL ARTICLES
Publication year
2024
Publication date
Feb 2024
Publisher
John Wiley & Sons, Inc.
e-ISSN
2051817X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2926327508
Copyright
© 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.