Real-time imaging of cGMP signaling shows pronounced differences between glomerular endothelial cells and podocytes

Recent clinical trials of drugs enhancing cyclic guanosine monophosphate (cGMP) signaling for cardiovascular diseases have renewed interest in cGMP biology within the kidney. However, the role of cGMP signaling in glomerular endothelial cells (GECs) and podocytes remains largely unexplored. Using ac...

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Bibliographic Details
Published in:Scientific reports 2024-10, Vol.14 (1), p.26099-12, Article 26099
Main Authors: Rutkowski, Nelli, Görlitz, Frederik, Wiesner, Eva, Binz-Lotter, Julia, Feil, Susanne, Feil, Robert, Benzing, Thomas, Hackl, Matthias J.
Format: Article
Language:English
Subjects:
631/1647/245/2225
631/1647/328
692/4022
692/4022/272
692/4022/272/1684/1587
692/4022/272/1684/1587/2101
Animals
Atrial Natriuretic Factor - metabolism
cGMP signaling
Cyclic GMP - metabolism
Endothelial Cells - drug effects
Endothelial Cells - metabolism
GECs
Glomerular endothelial cell
Guanylate Cyclase - metabolism
Humanities and Social Sciences
Kidney Glomerulus - cytology
Kidney Glomerulus - metabolism
Mice
multidisciplinary
pGC
Podocyte
Podocytes - metabolism
S-Nitroso-N-Acetylpenicillamine - pharmacology
Science
Science (multidisciplinary)
sGC
Signal Transduction
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Summary:Recent clinical trials of drugs enhancing cyclic guanosine monophosphate (cGMP) signaling for cardiovascular diseases have renewed interest in cGMP biology within the kidney. However, the role of cGMP signaling in glomerular endothelial cells (GECs) and podocytes remains largely unexplored. Using acute kidney slices from mice expressing the FRET-based cGMP biosensor cGi500 in endothelial cells or podocytes enabled real-time visualization of cGMP. Stimulation with atrial natriuretic peptide (ANP) or SNAP (NO donor) and various phosphodiesterase (PDE) inhibitors elevated intracellular cGMP in both cell types. GECs showed a transient cGMP response upon particulate or soluble guanylyl cyclase activation, while the cGMP response in podocytes reached a plateau following ANP administration. Co-stimulation (ANP + SNAP) led to an additive response in GECs. The administration of PDE inhibitors revealed a broader basal PDE activity in GECs dominated by PDE2a. In podocytes, basal PDE activity was mainly restricted to PDE3 and PDE5 activity. Our data demonstrate the existence of both guanylyl cyclase pathways in GECs and podocytes with cell-specific differences in cGMP synthesis and degradation, potentially suggesting new therapeutic options for kidney diseases.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-76768-1