Cargando…
The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations
The aim of the present study was to ascertain whether high sodium levels can directly promote the proliferation of vascular smooth muscle cells (VSMCs) and to elucidate the underlying mechanisms. Additional sodium chloride (NaCl) was added to the routine culture medium. Cell proliferation was evalua...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687433/ https://www.ncbi.nlm.nih.gov/pubmed/26530729 http://dx.doi.org/10.3892/ijmm.2015.2394 |
_version_ | 1782406633759965184 |
---|---|
author | WU, YAN ZHOU, JUAN WANG, HUAN WU, YUE GAO, QIYUE WANG, LIJUN ZHAO, QIANG LIU, PEINING GAO, SHANSHAN WEN, WEN ZHANG, WEIPING LIU, YAN YUAN, ZUYI |
author_facet | WU, YAN ZHOU, JUAN WANG, HUAN WU, YUE GAO, QIYUE WANG, LIJUN ZHAO, QIANG LIU, PEINING GAO, SHANSHAN WEN, WEN ZHANG, WEIPING LIU, YAN YUAN, ZUYI |
author_sort | WU, YAN |
collection | PubMed |
description | The aim of the present study was to ascertain whether high sodium levels can directly promote the proliferation of vascular smooth muscle cells (VSMCs) and to elucidate the underlying mechanisms. Additional sodium chloride (NaCl) was added to the routine culture medium. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. The mRNA expression level of proliferating cell nuclear antigen (PCNA) was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression levels of PCNA and phosphorylated c-Jun amino N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were measured by western blot analysis. Cell proliferation assay revealed that Na(+) rather than Cl(−) or osmotic pressure promoted the proliferation of the VSMCs. The high sodium level upregulated the expression of PCNA and the phosphorylation levels of JNK, ERK1/2 and p38 MAPK. The inhibition of JNK and ERK1/2 decreased PCNA expression. Of note, the inhibition of p38 MAPK using the inhibitor, SB203580, increased PCNA expression. However, when p38 MAPK was activated by anisomycin, PCNA expression was decreased. On the whole, our findings demonstrate that a relatively high sodium level per se directly promotes the proliferation of VSMCs through the JNK/ERK1/2/PCNA pathway. At the same time, this induction of the proliferation of VSMCs due to high sodium levels can be maintained at a low level via the activation of p38 MAPK. |
format | Online Article Text |
id | pubmed-4687433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-46874332015-12-31 The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations WU, YAN ZHOU, JUAN WANG, HUAN WU, YUE GAO, QIYUE WANG, LIJUN ZHAO, QIANG LIU, PEINING GAO, SHANSHAN WEN, WEN ZHANG, WEIPING LIU, YAN YUAN, ZUYI Int J Mol Med Articles The aim of the present study was to ascertain whether high sodium levels can directly promote the proliferation of vascular smooth muscle cells (VSMCs) and to elucidate the underlying mechanisms. Additional sodium chloride (NaCl) was added to the routine culture medium. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. The mRNA expression level of proliferating cell nuclear antigen (PCNA) was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression levels of PCNA and phosphorylated c-Jun amino N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were measured by western blot analysis. Cell proliferation assay revealed that Na(+) rather than Cl(−) or osmotic pressure promoted the proliferation of the VSMCs. The high sodium level upregulated the expression of PCNA and the phosphorylation levels of JNK, ERK1/2 and p38 MAPK. The inhibition of JNK and ERK1/2 decreased PCNA expression. Of note, the inhibition of p38 MAPK using the inhibitor, SB203580, increased PCNA expression. However, when p38 MAPK was activated by anisomycin, PCNA expression was decreased. On the whole, our findings demonstrate that a relatively high sodium level per se directly promotes the proliferation of VSMCs through the JNK/ERK1/2/PCNA pathway. At the same time, this induction of the proliferation of VSMCs due to high sodium levels can be maintained at a low level via the activation of p38 MAPK. D.A. Spandidos 2016-01 2015-10-27 /pmc/articles/PMC4687433/ /pubmed/26530729 http://dx.doi.org/10.3892/ijmm.2015.2394 Text en Copyright: © Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles WU, YAN ZHOU, JUAN WANG, HUAN WU, YUE GAO, QIYUE WANG, LIJUN ZHAO, QIANG LIU, PEINING GAO, SHANSHAN WEN, WEN ZHANG, WEIPING LIU, YAN YUAN, ZUYI The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
title | The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
title_full | The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
title_fullStr | The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
title_full_unstemmed | The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
title_short | The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
title_sort | activation of p38 mapk limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687433/ https://www.ncbi.nlm.nih.gov/pubmed/26530729 http://dx.doi.org/10.3892/ijmm.2015.2394 |
work_keys_str_mv | AT wuyan theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT zhoujuan theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wanghuan theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wuyue theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT gaoqiyue theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wanglijun theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT zhaoqiang theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT liupeining theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT gaoshanshan theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wenwen theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT zhangweiping theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT liuyan theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT yuanzuyi theactivationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wuyan activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT zhoujuan activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wanghuan activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wuyue activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT gaoqiyue activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wanglijun activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT zhaoqiang activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT liupeining activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT gaoshanshan activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT wenwen activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT zhangweiping activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT liuyan activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations AT yuanzuyi activationofp38mapklimitstheabnormalproliferationofvascularsmoothmusclecellsinducedbyhighsodiumconcentrations |