Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Induced by Urotensin II in Human Vascular Endothelial Cells

Park, Sung Lyea; Lee, Bo Kyung; Kim, Young Ae; Lee, Byung Ho; Jung, Yi Sook

doi:10.4062/biomolther.2013.051

Cited by 16 publications

(11 citation statements)

References 31 publications

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“…This increase is important for the risk of atherosclerosis or thrombosis as UT-II increases the expression of inflammatory mediators. Similar to this study, Park et al [31] showed that the UTR antagonist SB-657510 inhibited UT-II-induced expression of cytokines such as IL-1b and IL-6 in human vascular endothelial cells.…”

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confidence: 85%

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The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist

Palabıyık

Karakuş

Akpınar

et al. 2015

Basic Clin Pharma Tox

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We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor-alpha (TNF-a) and IL-1b and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre-treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre-treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti-inflammatory effects on high-dose PARA-induced hepatotoxicity in mice.

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supporting

confidence: 85%

“…Similar to this study, Park et al . showed that the UTR antagonist SB‐657510 inhibited UT‐II‐induced expression of cytokines such as IL‐1β and IL‐6 in human vascular endothelial cells.…”

mentioning

confidence: 99%

The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist

Palabıyık

Karakuş

Akpınar

et al. 2015

Basic Clin Pharma Tox

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“…, Park et al . ). Significant differences in the plasma levels of urotensin II, with a range of three or more orders of magnitude (from picomolar to nanomolar) have been reported across human studies in the literature, depending on the location of sampling and detection method (Ross et al .…”

Section: Discussionmentioning

confidence: 97%

Urotensin II promotes vagal‐mediated bradycardia by activating cardiac‐projecting parasympathetic neurons of nucleus ambiguus

Brailoiu

Deliu

Rabinowitz

et al. 2014

Journal of Neurochemistry

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Urotensin II (U-II) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U-II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U-II and its receptor at this level. We report here that U-II produces an increase in cytosolic Ca2+ concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca2+ release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptor; and (ii) Ca2+ influx through P/Q-type Ca2+ channels. In addition, U-II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U-II into nucleus ambiguus elicits dose-dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U-II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection.

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“…We also found that there was no significant dose-dependent effect of UII on HK-2 cells from 10 -5 -10 -9 mol/L, and 10 -7 mol/L was the concentration that produced the optimal effect. HK-2 cells were treated with UT antagonist, SB-657510, at the concentration of 10 -6 mol/L in accordance with Park et al 22.…”

Section: Cell Culturementioning

confidence: 97%

Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

Chen

Pang

et al. 2016

J of Diabetes Invest

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Aims/Introduction: Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in the kidney, and its effect in diabetes. Materials and Methods: Immunohistochemistry and western blot were carried out on the kidney tissues of diabetic UII receptor (UT) gene knockout mice, wild-type diabetic mice and normal control mice. For the in vitro experiment, HK-2 cells were treated with UII (10 -7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10 -6 mol/L) or autophagy inducer, rapamycin (10 -3 mol/L), for 12 h. Markers for autophagy (LC3-II, p62/ SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. Results: In diabetic UT knockout mice, expression of LC3-II is increased and p62 was reduced in comparison with that of the normal diabetic mice. Fibronectin and collagen IV were downregulated in diabetic UT knockout mice when compared with that of the normal diabetic mice. For the in vitro cell experiment, UII was shown to inhibit expression LC3-II and increase expression of p62 in comparison with that of the normal control. Treatment with SB-657510 can block UII-induced downregulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer, rapamycin, also inhibited UII-induced upregulation of fibronectin and collagen IV.Conclusions: The present study is the first to show that UII can downregulate autophagy in the kidney while accompanying the increased production of extracellular matrix in early diabetes. Our in vitro study also showed that upregulation of autophagy can decrease UII-induced production of extracellular matrix in HK-2 cells.

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Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Induced by Urotensin II in Human Vascular Endothelial Cells

Cited by 16 publications

References 31 publications

The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist

The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist

Urotensin II promotes vagal‐mediated bradycardia by activating cardiac‐projecting parasympathetic neurons of nucleus ambiguus

Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

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