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Article

RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells

1
Department of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, Heidelberg University, 69120 Heidelberg, Germany
2
NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
3
Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
4
The Ottawa Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
5
European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alexander E. Kalyuzhny
Cells 2021, 10(7), 1748; https://doi.org/10.3390/cells10071748
Received: 28 May 2021 / Revised: 25 June 2021 / Accepted: 7 July 2021 / Published: 11 July 2021
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in Germany)
The regulator of G-protein signaling 5 (RGS5) acts as an inhibitor of Gαq/11 and Gαi/o activity in vascular smooth muscle cells (VSMCs), which regulate arterial tone and blood pressure. While RGS5 has been described as a crucial determinant regulating the VSMC responses during various vascular remodeling processes, its regulatory features in resting VSMCs and its impact on their phenotype are still under debate and were subject of this study. While Rgs5 shows a variable expression in mouse arteries, neither global nor SMC-specific genetic ablation of Rgs5 affected the baseline blood pressure yet elevated the phosphorylation level of the MAP kinase ERK1/2. Comparable results were obtained with 3D cultured resting VSMCs. In contrast, overexpression of RGS5 in 2D-cultured proliferating VSMCs promoted their resting state as evidenced by microarray-based expression profiling and attenuated the activity of Akt- and MAP kinase-related signaling cascades. Moreover, RGS5 overexpression attenuated ERK1/2 phosphorylation, VSMC proliferation, and migration, which was mimicked by selectively inhibiting Gαi/o but not Gαq/11 activity. Collectively, the heterogeneous expression of Rgs5 suggests arterial blood vessel type-specific functions in mouse VSMCs. This comprises inhibition of acute agonist-induced Gαq/11/calcium release as well as the support of a resting VSMC phenotype with low ERK1/2 activity by suppressing the activity of Gαi/o. View Full-Text
Keywords: RGS proteins; G-protein signaling; VSMC phenotype; ERK1/2; blood pressure RGS proteins; G-protein signaling; VSMC phenotype; ERK1/2; blood pressure
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MDPI and ACS Style

Demirel, E.; Arnold, C.; Garg, J.; Jäger, M.A.; Sticht, C.; Li, R.; Kuk, H.; Wettschureck, N.; Hecker, M.; Korff, T. RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells. Cells 2021, 10, 1748. https://doi.org/10.3390/cells10071748

AMA Style

Demirel E, Arnold C, Garg J, Jäger MA, Sticht C, Li R, Kuk H, Wettschureck N, Hecker M, Korff T. RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells. Cells. 2021; 10(7):1748. https://doi.org/10.3390/cells10071748

Chicago/Turabian Style

Demirel, Eda, Caroline Arnold, Jaspal Garg, Marius A. Jäger, Carsten Sticht, Rui Li, Hanna Kuk, Nina Wettschureck, Markus Hecker, and Thomas Korff. 2021. "RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells" Cells 10, no. 7: 1748. https://doi.org/10.3390/cells10071748

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