| Online-Ressource |
Verfasst von: | Freundt, Greta [VerfasserIn]  |
| Samson-Himmelstjerna, Friedrich Alexander von [VerfasserIn]  |
| Nitz, Jan-Thorge [VerfasserIn]  |
| Lüdde, Mark [VerfasserIn]  |
| Waltenberger, Johannes [VerfasserIn]  |
| Wieland, Thomas [VerfasserIn]  |
| Frey, Norbert [VerfasserIn]  |
| Preusch, Michael [VerfasserIn]  |
| Hippe, Hans-Jörg [VerfasserIn]  |
Titel: | The orphan receptor GPRC5B activates pro-inflammatory signaling in the vascular wall via Fyn and NFκB |
Verf.angabe: | Greta Verena Freundt, Friedrich Alexander von Samson-Himmelstjerna, Jan-Thorge Nitz, Mark Luedde, Johannes Waltenberger, Thomas Wieland, Norbert Frey, Michael Preusch, Hans-Joerg Hippe |
E-Jahr: | 2022 |
Jahr: | 12 February 2022 |
Umfang: | 7 S. |
Fussnoten: | Online verfügbar: 7. Januar 2022, Artikelversion: 13. Januar 2022 ; Gesehen am 06.12.2022 |
Titel Quelle: | Enthalten in: Biochemical and biophysical research communications |
Ort Quelle: | [Amsterdam] : Elsevier B.V., 1959 |
Jahr Quelle: | 2022 |
Band/Heft Quelle: | 592(2022), Seite 60-66 |
ISSN Quelle: | 1090-2104 |
Abstract: | Background and aims: Atherosclerosis is driven by an inflammatory process of the vascular wall. The novel orphan G-protein coupled receptor 5B of family C (GPRC5B) is involved in drosophila sugar and lipid metabolism as well as mice adipose tissue inflammation. Here, we investigated the role of GPRC5B in the pro-atherogenic mechanisms of hyperglycemia and vascular inflammation. Methods: Immortalized and primary endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) were used for stimulation with high glucose or different cytokines. Adenoviral-or plasmid-driven GPRC5B overexpression and siRNA-mediated knockdown were performed in these cells to analyze functional and mechanistic pathways of GPRC5B. Results: In ECs and VSMCs, stimulation with high glucose, TNFa or LPS induced a significant upregulation of endogenous GPRC5B mRNA and protein levels. GPRC5B overexpression and knockdown increased and attenuated, respectively, the expression of the pro-inflammatory cytokines TNFa, IL-1b, IL-6 as well as the pro-atherogenic vascular adhesion molecules ICAM-1 and VCAM-1. Furthermore, the expression and activity of the metalloproteinase MMP-9, a component of atherosclerotic plaque stabilization, were significantly enhanced by GPRC5B overexpression. Mechanistically, GPRC5B increased the phosphorylation of ERK1/2 and activated NFkB through a direct interaction with the tyrosine kinase Fyn. Conclusions: Our findings demonstrate that GPRC5B is upregulated in response to high glucose and pro inflammatory signaling. GPRC5B functionally modulates the inflammatory activity in cells of the vascular wall, suggesting a pro-atherogenic GPRC5B-dependent positive feedback loop via Fyn and NFkB. Thus, GPRC5B warrants further attention as a novel pharmacological target for the treatment of vascular inflammation and possibly atherogenesis. (c) 2022 Elsevier Inc. All rights reserved. |
DOI: | doi:10.1016/j.bbrc.2022.01.009 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.bbrc.2022.01.009 |
| Volltext: https://linkinghub.elsevier.com/retrieve/pii/S0006291X22000171 |
| DOI: https://doi.org/10.1016/j.bbrc.2022.01.009 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Atherosclerosis |
| cells |
| gpcr |
| gprc5b |
| high glucose |
| Hyperglycemia |
| protein-coupled receptor |
| transduction |
| Vascular inflammation |
K10plus-PPN: | 1824515278 |
Verknüpfungen: | → Zeitschrift |
¬The¬ orphan receptor GPRC5B activates pro-inflammatory signaling in the vascular wall via Fyn and NFκB / Freundt, Greta [VerfasserIn]; 12 February 2022 (Online-Ressource)