Jensen, Mia and Heinl, Elena-Sofia and Federlein, Anna and Schwartz, Uwe and Lund, Lars and Madsen, Kirsten and Jensen, Boye L. and Schweda, Frank (2024) Identification of natriuretic peptide receptor A-related gene expression signatures in podocytes in vivo reveals baseline control of protective pathways. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 327 (5). F806-F821. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
Natriuretic peptide receptor-A (NPR-A) is the principal receptor for the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Targeted deletion of NPR-A in mouse glomerular podocytes significantly enhances renal injury in vivo in the DOCA-salt experimental model. It was therefore hypothesized that natriuretic peptides exert a direct protective effect on glomerular barrier integrity through activation of NPR-A and modulation of gene expression patterns in podocytes. Green fluorescence-positive podocytes from mice with a conditional deletion of Npr1 encoding NPR-A were isolated by fluorescence-activated cell sorting (FACS). Differentially expressed genes (DEGs) in podocytes were identified by RNA sequencing of podocytes from wild-type and NPR-A-deleted mice. Enrichment analysis was performed on the DEGs using Gene Ontology (GO) terms. Identified transcripts were validated by real-time PCR and ELISA of cultured isolated human and mouse glomeruli. In addition, the effect of natriuretic peptides on podocyte migration was investigated by measuring the outgrowth of podocytes from cultured glomeruli. A total of 158 DEGs were identified with 81 downregulated DEGs and 77 upregulated DEGs in Npr1-deficient podocytes. Among the downregulated genes were protein S and semaphorin 3G, which are known to have protective effects in podocytes. Protein S was also expressed in and secreted from isolated human glomeruli. GO enrichment analysis revealed that the upregulated DEGs in NPR-A deficient podocytes were associated with cell migration and motility. In line, BNP significantly decreased podocyte outgrowth from cultured glomeruli. In conclusion, endogenous levels of natriuretic peptides in mice support baseline protective pathways at glomerular podocytes such as protein S and suppress podocyte migration.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GUANYLYL CYCLASE-A; CHRONIC KIDNEY-DISEASE; MICE; CELLS; OVEREXPRESSION; DISRUPTION; FIBROSIS; SULFATE; INJURY; ROLES; glomerular filtration barrier; kidney; migration; natriuretic peptides; protection |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Oct 2025 09:53 |
| Last Modified: | 07 Oct 2025 09:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64147 |
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