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Status: Bibliographieeintrag

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Verfasst von:Freundt, Greta [VerfasserIn]   i
 Samson-Himmelstjerna, Friedrich Alexander von [VerfasserIn]   i
 Nitz, Jan-Thorge [VerfasserIn]   i
 Lüdde, Mark [VerfasserIn]   i
 Waltenberger, Johannes [VerfasserIn]   i
 Wieland, Thomas [VerfasserIn]   i
 Frey, Norbert [VerfasserIn]   i
 Preusch, Michael [VerfasserIn]   i
 Hippe, Hans-Jörg [VerfasserIn]   i
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

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