scholarly journals Downregulation of Thromboxane A2 Receptor Occurs Mainly via Nuclear Factor-KappaB Signaling Pathway in Rat Renal Artery

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Yaping Zhang ◽  
Man Mi ◽  
Yan-Hua Xie ◽  
Si-Wang Wang ◽  
Lars Edvinsson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Renal Artery ◽  
Signaling Pathway ◽  
Contractile Response ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Receptor Mrna ◽  
Tp Receptor ◽  
Tp Receptors ◽  
Specific Inhibitors

Thromboxane A2 (TXA2) acts on TXA2 receptors (TP) to regulate renal artery blood flow and subsequently contributes to the pathogenesis of renal ischemia. The present study was designed to examine if nuclear factor-kappaB (NF-κB) signaling pathway is involved in the downregulation of TP receptors in rat renal artery. Rat renal artery segments were organ cultured for 6 or 24 h. Downregulation of TP receptors was monitored using myograph (contractile function), real-time PCR (receptor mRNA), and immunohistochemistry (receptor protein). Specific inhibitors (MG-132 and BMS345541) for NF-κB signaling pathway were used to dissect the underlying molecular mechanisms involved. Compared to fresh (noncultured) segments, organ culture of the renal artery segments for 24 h induced a significant rightward shift of U46619 (TP receptor agonist) contractile response curves (pEC50: 6.89±0.06 versus 6.48±0.04, P<0.001). This decreased contractile response to U46619 was paralleled with decreased TP receptor mRNA and protein expressions in the renal artery smooth muscle cells. Specific inhibitors (MG-132 and BMS345541) for NF-κB signaling pathway significantly abolished the decreased TP protein expression and receptor-mediated contractions. In conclusion, downregulation of TP receptors in the renal artery smooth muscle cells occurs mainly via the NF-κB signaling pathway.

Regulation of Nuclear Factor-KappaB (NF-κB) signaling pathway by non-coding RNAs in cancer: Inhibiting or promoting carcinogenesis?

2021 ◽  
Vol 509 ◽  
pp. 63-80 ◽  
Author(s):  
Sepideh Mirzaei ◽  
Ali Zarrabi ◽  
Farid Hashemi ◽  
Amirhossein Zabolian ◽  
Hossein Saleki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Non Coding Rnas

Prostanoid and TP-receptors in atherothrombosis: Is there a role for their antagonism?

2010 ◽  
Vol 104 (11) ◽  
pp. 949-954 ◽  
Author(s):  
Chiara Giannarelli ◽  
M. Urooj Zafar ◽  
Juan Badimon
Keyword(s):  
Smooth Muscle ◽  
Endothelial Dysfunction ◽  
Platelet Activation ◽  
Critical Role ◽  
Clinical Manifestations ◽  
Plaque Burden ◽  
Platelet Activity ◽  
Tp Receptor ◽  
Tp Receptors ◽  
Plaque Stabilisation

SummaryAtherosclerosis and its clinical manifestations (i.e. myocardial infarction, stroke) are major causes of mortality and morbidity in Western countries. Endothelial dysfunction is considered the first step in the cascade leading up to coronary events. Increasing evidence suggests that direct inhibition of thromboxane A2/prostaglandin (TP)-receptors may not only have anti-platelet effects but also impact endothelial dysfunction as well as inflammatory component of atherosclerosis. While TP-receptor involvement in platelet function has received the greatest attention, more recent findings support the critical role of TP-receptor in other pathophysiological aspects of atherothrombosis. Prostanoids (i.e. TxA2, F2-isoprostanes, prostaglandins endoperoxides PGG2/PGH2) are known to promote the initiation and progression of atherosclerosis, not only via platelet activation, but through leukocyte-endothelial interactions and vasoconstriction. Dysfunctional endothelium, characterised by increased COX-activity, releases prostanoids that promote endothelial exposure to adhesion molecules and induce smooth muscle cell contraction. Plaque macrophages synthesise PGH2/PGG2 via COX-2; these potent prostanoids can trigger platelet activation and aggregation despite COX-1 inhibition by aspirin. TP-receptor inhibition has been reported to exert anti-atherosclerotic effects in pre-clinical model of disease. Reduction of plaque burden was associated with plaque stabilisation documented by the reduction in the content of macrophages, apoptotic cells, MMPs and endothelin-1, and the increase in smooth muscle cells content. TP-receptor blockade might have an anti-athero-sclerotic and plaque stabilisation effect. The possibility of combining anti-platelet activity with an anti-atherosclerotic effect via selective TP-receptor inhibitors could have important implications especially in clinical conditions associated with increased production of prostanoids, such as diabetes.

scholarly journals Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells

2015 ◽  
Vol 21 (11) ◽  
pp. 865-883 ◽  
Author(s):  
Victoria J. Cookson ◽  
Sarah L. Waite ◽  
Paul R. Heath ◽  
Paul J. Hurd ◽  
Saurabh V. Gandhi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Promoter Regions

Activation of nuclear factor-kappaB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex

2005 ◽  
Vol 93 (1) ◽  
pp. 26-37 ◽  
Author(s):  
Xiaoming Hu ◽  
Olivera Nesic-Taylor ◽  
Jingxin Qiu ◽  
Harriett C. Rea ◽  
Roderick Fabian ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interleukin 1 ◽  
Rat Hippocampus ◽  
Neonatal Rat ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Hypoxia Ischemia

Abstract 520: Thromboxane Receptors in Smooth Muscle Promote Hypertension, Vascular Remodeling and Sudden Death

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Matthew A Sparks ◽  
Natalia Makhanova ◽  
Robert C Griffiths ◽  
John N Snouwaert ◽  
Beverly Koller ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Sudden Death ◽  
Smooth Muscle Cells ◽  
Vascular Remodeling ◽  
Muscle Cells ◽  
Link Type ◽  
Tp Receptor ◽  
Induced Hypertension ◽  
Tp Receptors

The prostanoid thromboxane (TxA2) is a potent vasoconstrictor and platelet aggregant that has been implicated in the pathogenesis of cardiovascular diseases including hypertension. Actions of thromboxane (TP) receptors in platelets and the vasculature have both been implicated in cardiovascular pathogenesis. To distinguish the contributions of vascular TP receptors in isolation, we generated mice with cell-specific deletion of TP receptors in smooth muscle cells (TP-SMKOs) using Cre/Loxp technology. We used the KISM22α-Cre transgenic mouse line, with Cre recombinase “knocked-in” to the Sm22α gene locus, to excise the conditional Tp receptor allele specifically in smooth muscle. mRNA for the TP-receptor was easily detected in aortae from control mice, but not from TP-SMKOs (P<0.005). Similarly, TP receptor mRNA expression in mesenteric arteries, with intact endothelium and adventitia, was decreased by ≈80% in TP-SMKOs (P=0.05). In TP-SMKOs, acute vasoconstrictor responses to the TP agonist U46619 were dramatically attenuated by ≈60% in both the peripheral and renal circulations (P<0.05), whereas acute vascular responses to angiotensin II were unaffected. Infusion of high-dose U46619 caused circulatory collapse and death in a majority of control mice, but TP-SMKOs were completely protected from U46619 -induced sudden death (P<0.05). Baseline blood pressures measured by radiotelemetry were similar in TP-SMKOs (111±1 mmHg) and Controls (114±1 mmHg; P=NS). However, the absence of TP receptors in vascular smooth muscle cells caused significant attenuation of angiotensin II-induced hypertension (controls: 159±2 mm Hg; TP-SMKO: 145±8 mm Hg, P<0.05) and diminished aortic medial hypertrophy in TP-SMKOs (59±4 μm) vs. Controls (79±7 μm; P<0.05). Thus, vascular TP receptors play a major role in shock, angiotensin II-induced hypertension, and vascular remodeling.

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