scholarly journals Rgs5 Targeting Leads to Chronic Low Blood Pressure and a Lean Body Habitus

2008 ◽  
Vol 28 (8) ◽  
pp. 2590-2597 ◽  
Author(s):  
Hyeseon Cho ◽  
Chung Park ◽  
Il-Young Hwang ◽  
Sang-Bae Han ◽  
Dan Schimel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
G Protein ◽  
Muscle Cells ◽  
Cardiovascular Development ◽  
Protein Signaling ◽  
Body Habitus ◽  
Low Blood Pressure

ABSTRACT RGS5 is a potent GTPase-activating protein for Giα and Gqα that is expressed strongly in pericytes and is present in vascular smooth muscle cells. To study the role of RGS5 in blood vessel physiology, we generated Rgs5-deficient mice. The Rgs5 −/− mice developed normally, without obvious defects in cardiovascular development or function. Surprisingly, Rgs5 −/− mice had persistently low blood pressure, lower in female mice than in male mice, without concomitant cardiac dysfunction, and a lean body habitus. The examination of the major blood vessels revealed that the aortas of Rgs5 −/− mice were dilated compared to those of control mice, without altered wall thickness. Isolated aortic smooth muscle cells from the Rgs5 −/− mice exhibited exaggerated levels of phosphorylation of vasodilator-stimulated phosphoprotein and extracellular signal-regulated kinase in response to stimulation with either sodium nitroprusside or sphingosine 1-phosphate. The results of this study, along with those of previous studies demonstrating that RGS5 stability is under the control of nitric oxide via the N-end rule pathway, suggest that RGS5 may balance vascular tone by attenuating vasodilatory signaling in vivo in opposition to RGS2, another RGS (regulator of G protein signaling) family member known to inhibit G protein-coupled receptor-mediated vasoconstrictor signaling. Blocking the function or the expression of RGS5 may provide an alternative approach to treat hypertension.

scholarly journals Olfactory receptor Olfr78 (prostate-specific G protein-coupled receptor PSGR) expression in arterioles supplying skeletal and cardiac muscles and in arterioles feeding some murine organs

2021 ◽  
Author(s):  
Petra Mermer ◽  
Jörg Strotmann ◽  
Wolfgang Kummer ◽  
Renate Paddenberg
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
G Protein ◽  
Olfactory Receptor ◽  
Muscle Cells ◽  
Striated Muscles ◽  
Pressure Regulation ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

AbstractThe olfactory receptor Olfr78 (prostate-specific G protein-coupled receptor PSGR) is a member of the G protein-coupled receptor family mediating olfactory chemosensation, but it is additionally expressed in other tissues. Olfr78 expressed in kidney participates in blood pressure regulation, and in prostate it plays a role in the development of cancer. We here screened many organs/tissues of transgenic mice co-expressing β-galactosidase with Olfr78. X-gal-positive cells were detectable in smooth muscle cells of numerous arterioles of striated muscles (heart ventricles and skeletal muscles of various embryological origin). In addition, in most organs where we found expression of Olfr78 mRNA, X-gal staining was restricted to smooth muscle cells of small blood vessels. The dominant expression of Olfr78 in arteriolar smooth muscle cells supports the concept of an important role in blood pressure regulation and suggests a participation in the fine tuning of blood supply especially of striated muscles. This should be considered when targeting Olfr78 in other contexts such as prostate cancer.

scholarly journals RNA-binding protein HuR regulates RGS4 mRNA stability in rabbit colonic smooth muscle cells

2010 ◽  
Vol 299 (6) ◽  
pp. C1418-C1429 ◽  
Author(s):  
Fang Li ◽  
Danielle Y. Hu ◽  
Shu Liu ◽  
Sunila Mahavadi ◽  
William Yen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
G Protein ◽  
Mrna Stability ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Muscle Cells ◽  
G Protein Signaling ◽  
Protein Signaling

Regulator of G protein signaling 4 (RGS4) regulates the strength and duration of G protein signaling and plays an important role in smooth muscle contraction, cardiac development, and psychiatric disorders. Little is known about the posttranscriptional regulation of RGS4 expression. We cloned the full-length cDNA of rabbit RGS4, which contains a long 3′-untranslated region (UTR) with several AU-rich elements (AREs). We determined whether RGS4 mRNA stability is mediated by the RNA-binding protein human antigen R (HuR) and contributes to IL-1β-induced upregulation of RGS4 expression. We show that IL-1β treatment in colonic smooth muscle cells doubled the half-life of RGS4 mRNA. Addition of RGS4 3′-UTR to the downstream of Renilla luciferase reporter induced dramatic reduction in the enzyme activity and mRNA expression of luciferase, which was attenuated by the site-directed mutation of the two 3′-most ARE sites. IL-1β increased luciferase mRNA stability in a UTR-dependent manner. Knockdown of HuR significantly aggravated UTR-mediated instability of luciferase and inhibited IL-1β-induced upregulation of RGS4 mRNA. In addition, IL-1β increased cytosolic translocation and RGS4 mRNA binding of HuR. These findings suggest that 3′-most ARE sites within RGS4 3′-UTR are essential for the instability of RGS4 mRNA and IL-1β promotes the stability of RGS4 mRNA through HuR.

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

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1748
Author(s):  
Eda Demirel ◽  
Caroline Arnold ◽  
Jaspal Garg ◽  
Marius Andreas Jäger ◽  
Carsten Sticht ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Genetic Ablation ◽  
Variable Expression ◽  
Arterial Blood

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.

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