Universität zu Köln

Rutkowski, Nelli ORCID: 0000-0003-3672-4310, Görlitz, Frederik, Wiesner, Eva ORCID: 0000-0002-4096-6374, Binz-Lotter, Julia ORCID: 0000-0003-4678-0703, Feil, Susanne, Feil, Robert, Benzing, Thomas ORCID: 0000-0003-0512-1066 and Hackl, Matthias J. ORCID: 0000-0002-4199-3374 (2024). Real-time imaging of cGMP signaling shows pronounced differences between glomerular endothelial cells and podocytes. Scientific Reports, 14 (1). pp. 1-12. Springer Nature. ISSN 2045-2322

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Abstract

[Artikel-Nr.: 26099] 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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Rutkowski, Nelli UNSPECIFIED https://orcid.org/0000-0003-3672-4310 UNSPECIFIED Görlitz, Frederik UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Eva UNSPECIFIED https://orcid.org/0000-0002-4096-6374 UNSPECIFIED Binz-Lotter, Julia UNSPECIFIED https://orcid.org/0000-0003-4678-0703 UNSPECIFIED Feil, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Feil, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED https://orcid.org/0000-0003-0512-1066 UNSPECIFIED Hackl, Matthias J. UNSPECIFIED https://orcid.org/0000-0002-4199-3374 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-815954
Identification Number:	10.1038/s41598-024-76768-1
Journal or Publication Title:	Scientific Reports
Volume:	14
Number:	1
Page Range:	pp. 1-12
Date:	30 October 2024
Publisher:	Springer Nature
ISSN:	2045-2322
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Innere Medizin > Klinik II für Innere Medizin - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language cGMP signaling ; sGC ; pGC ; Podocyte ; Glomerular endothelial cell ; GECs ; cGi500 ; FRET English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81595