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

Zhang, Yaping LU ; Mi, Man-Tian; Xie, Yan-hua; Wang, Si-wang; Edvinsson, Lars LU and Xu, Cang Bao LU (2017) In Advances in Pharmacological Sciences 2017.
Abstract

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-B) 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-B signaling pathway were used to dissect the underlying molecular mechanisms involved. Compared to fresh (noncultured)... (More)

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-B) 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-B 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-B 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-B signaling pathway.

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publication status
published
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in
Advances in Pharmacological Sciences
volume
2017
external identifiers
  • scopus:85026555142
  • wos:000405332800001
ISSN
1687-6334
DOI
10.1155/2017/6507048
language
English
LU publication?
yes
id
ad495f6a-8057-4c8c-a983-fddf944851c0
date added to LUP
2017-08-24 15:41:20
date last changed
2017-09-18 11:43:02
@article{ad495f6a-8057-4c8c-a983-fddf944851c0,
  abstract     = {<p>Thromboxane A<sub>2</sub> (TXA<sub>2</sub>) acts on TXA<sub>2</sub> 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-B) 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-B 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 (pEC<sub>50</sub>: 6.89±0.06 versus 6.48±0.04, P&lt;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-B 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-B signaling pathway.</p>},
  articleno    = {6507048},
  author       = {Zhang, Yaping and Mi, Man-Tian and Xie, Yan-hua and Wang, Si-wang and Edvinsson, Lars and Xu, Cang Bao},
  issn         = {1687-6334},
  language     = {eng},
  series       = {Advances in Pharmacological Sciences},
  title        = {Downregulation of Thromboxane A<sub>2</sub> Receptor Occurs Mainly via Nuclear Factor-KappaB Signaling Pathway in Rat Renal Artery},
  url          = {http://dx.doi.org/10.1155/2017/6507048},
  volume       = {2017},
  year         = {2017},
}