Nuclear Factor-kappaB-Mediated Endothelin Receptor Up-Regulation Increases Renal Artery Contractility in Rats
(2013) In Basic & Clinical Pharmacology & Toxicology 113(6). p.401-410- Abstract
- Increased renal artery contractility leads to renal vasospasm and ischaemia as well as kidney damage. This study was designed to examine the hypothesis that organ culture of renal arteries induces transcriptional up-regulation of endothelin type A (ETA) and type B2 (ETB2) receptors in the smooth muscle cells via activation of nuclear factor-kappaB (NF-B) and subsequently increases renal artery contractility. Rat renal artery segments were organ-cultured for 6 or 24hr to increase endothelin receptor-mediated contraction. To dissect molecular mechanisms involved in this process, inhibitors for NF-B signalling pathway (MG-132 and BMS345541), transcription (actinomycin D) and translation (cycloheximide) were used during organ culture.... (More)
- Increased renal artery contractility leads to renal vasospasm and ischaemia as well as kidney damage. This study was designed to examine the hypothesis that organ culture of renal arteries induces transcriptional up-regulation of endothelin type A (ETA) and type B2 (ETB2) receptors in the smooth muscle cells via activation of nuclear factor-kappaB (NF-B) and subsequently increases renal artery contractility. Rat renal artery segments were organ-cultured for 6 or 24hr to increase endothelin receptor-mediated contraction. To dissect molecular mechanisms involved in this process, inhibitors for NF-B signalling pathway (MG-132 and BMS345541), transcription (actinomycin D) and translation (cycloheximide) were used during organ culture. Endothelin receptors were studied using a sensitive myograph (functional contractility), real-time PCR (mRNA analysis) and immunohistochemistry (protein localization). Compared with fresh segments, contractile responses to endothelin-1 (non-selective endothelin receptor agonist) and sarafotoxin 6c (selective ETB receptor agonist) were significantly increased in the segments after 24hr of organ culture; ETB2 receptor-mediated maximal contraction increased from 2.7 +/- 0.5 to 135.3 +/- 5.1 (p<0.001), and potency (pEC(50)) of ETA receptor agonist increased from 8.20 +/- 0.04 to 8.72 +/- 0.07 (p<0.001). This was in parallel with increased corresponding mRNA and protein expression for ETA and ETB2 receptors. BMS345541, MG-132, actinomycin D or cyclohexamide, respectively, suppressed the up-regulation of ETA and ETB2 receptors. Immunostaining performed with specific antibody showed that IB was phosphorylated during organ culture. In conclusion, activation of NF-B mediates up-regulation of ETA and ETB2 receptors and subsequently increases renal artery contractility, which may contribute to renal vasospasm and ischaemia as well as kidney damage. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4196498
- author
- Xie, Yan-Hua ; Wang, Si-Wang ; Zhang, Yaping ; Edvinsson, Lars LU and Xu, Cang-Bao LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Basic & Clinical Pharmacology & Toxicology
- volume
- 113
- issue
- 6
- pages
- 401 - 410
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000327024300006
- scopus:84887822325
- pmid:24034179
- ISSN
- 1742-7843
- DOI
- 10.1111/bcpt.12123
- language
- English
- LU publication?
- yes
- id
- 3cfbe833-342e-491b-a3e8-7c90b9d57c98 (old id 4196498)
- date added to LUP
- 2016-04-01 10:28:07
- date last changed
- 2024-01-21 15:04:21
@article{3cfbe833-342e-491b-a3e8-7c90b9d57c98,
abstract = {{Increased renal artery contractility leads to renal vasospasm and ischaemia as well as kidney damage. This study was designed to examine the hypothesis that organ culture of renal arteries induces transcriptional up-regulation of endothelin type A (ETA) and type B2 (ETB2) receptors in the smooth muscle cells via activation of nuclear factor-kappaB (NF-B) and subsequently increases renal artery contractility. Rat renal artery segments were organ-cultured for 6 or 24hr to increase endothelin receptor-mediated contraction. To dissect molecular mechanisms involved in this process, inhibitors for NF-B signalling pathway (MG-132 and BMS345541), transcription (actinomycin D) and translation (cycloheximide) were used during organ culture. Endothelin receptors were studied using a sensitive myograph (functional contractility), real-time PCR (mRNA analysis) and immunohistochemistry (protein localization). Compared with fresh segments, contractile responses to endothelin-1 (non-selective endothelin receptor agonist) and sarafotoxin 6c (selective ETB receptor agonist) were significantly increased in the segments after 24hr of organ culture; ETB2 receptor-mediated maximal contraction increased from 2.7 +/- 0.5 to 135.3 +/- 5.1 (p<0.001), and potency (pEC(50)) of ETA receptor agonist increased from 8.20 +/- 0.04 to 8.72 +/- 0.07 (p<0.001). This was in parallel with increased corresponding mRNA and protein expression for ETA and ETB2 receptors. BMS345541, MG-132, actinomycin D or cyclohexamide, respectively, suppressed the up-regulation of ETA and ETB2 receptors. Immunostaining performed with specific antibody showed that IB was phosphorylated during organ culture. In conclusion, activation of NF-B mediates up-regulation of ETA and ETB2 receptors and subsequently increases renal artery contractility, which may contribute to renal vasospasm and ischaemia as well as kidney damage.}},
author = {{Xie, Yan-Hua and Wang, Si-Wang and Zhang, Yaping and Edvinsson, Lars and Xu, Cang-Bao}},
issn = {{1742-7843}},
language = {{eng}},
number = {{6}},
pages = {{401--410}},
publisher = {{Wiley-Blackwell}},
series = {{Basic & Clinical Pharmacology & Toxicology}},
title = {{Nuclear Factor-kappaB-Mediated Endothelin Receptor Up-Regulation Increases Renal Artery Contractility in Rats}},
url = {{http://dx.doi.org/10.1111/bcpt.12123}},
doi = {{10.1111/bcpt.12123}},
volume = {{113}},
year = {{2013}},
}