Real-time imaging of cGMP signaling shows pronounced differences between glomerular endothelial cells and podocytes.
FRET
GECs
Glomerular endothelial cell
Podocyte
cGMP signaling
cGi500
pGC
sGC
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2024
30 10 2024
Historique:
received:
09
07
2024
accepted:
16
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39478086
doi: 10.1038/s41598-024-76768-1
pii: 10.1038/s41598-024-76768-1
doi:
Substances chimiques
Cyclic GMP
H2D2X058MU
Atrial Natriuretic Factor
85637-73-6
S-Nitroso-N-Acetylpenicillamine
79032-48-7
Guanylate Cyclase
EC 4.6.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26099Informations de copyright
© 2024. The Author(s).
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