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The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations

  • Authors:
    • Yan Wu
    • Juan Zhou
    • Huan Wang
    • Yue Wu
    • Qiyue Gao
    • Lijun Wang
    • Qiang Zhao
    • Peining Liu
    • Shanshan Gao
    • Wen Wen
    • Weiping Zhang
    • Yan Liu
    • Zuyi Yuan
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 74-82
    |
    Published online on: October 27, 2015
       https://doi.org/10.3892/ijmm.2015.2394
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Wu Y, Zhou J, Wang H, Wu Y, Gao Q, Wang L, Zhao Q, Liu P, Gao S, Wen W, Wen W, et al: The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations. Int J Mol Med 37: 74-82, 2016.
APA
Wu, Y., Zhou, J., Wang, H., Wu, Y., Gao, Q., Wang, L. ... Yuan, Z. (2016). The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations. International Journal of Molecular Medicine, 37, 74-82. https://doi.org/10.3892/ijmm.2015.2394
MLA
Wu, Y., Zhou, J., Wang, H., Wu, Y., Gao, Q., Wang, L., Zhao, Q., Liu, P., Gao, S., Wen, W., Zhang, W., Liu, Y., Yuan, Z."The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations". International Journal of Molecular Medicine 37.1 (2016): 74-82.
Chicago
Wu, Y., Zhou, J., Wang, H., Wu, Y., Gao, Q., Wang, L., Zhao, Q., Liu, P., Gao, S., Wen, W., Zhang, W., Liu, Y., Yuan, Z."The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations". International Journal of Molecular Medicine 37, no. 1 (2016): 74-82. https://doi.org/10.3892/ijmm.2015.2394
Copy and paste a formatted citation
x
Spandidos Publications style
Wu Y, Zhou J, Wang H, Wu Y, Gao Q, Wang L, Zhao Q, Liu P, Gao S, Wen W, Wen W, et al: The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations. Int J Mol Med 37: 74-82, 2016.
APA
Wu, Y., Zhou, J., Wang, H., Wu, Y., Gao, Q., Wang, L. ... Yuan, Z. (2016). The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations. International Journal of Molecular Medicine, 37, 74-82. https://doi.org/10.3892/ijmm.2015.2394
MLA
Wu, Y., Zhou, J., Wang, H., Wu, Y., Gao, Q., Wang, L., Zhao, Q., Liu, P., Gao, S., Wen, W., Zhang, W., Liu, Y., Yuan, Z."The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations". International Journal of Molecular Medicine 37.1 (2016): 74-82.
Chicago
Wu, Y., Zhou, J., Wang, H., Wu, Y., Gao, Q., Wang, L., Zhao, Q., Liu, P., Gao, S., Wen, W., Zhang, W., Liu, Y., Yuan, Z."The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations". International Journal of Molecular Medicine 37, no. 1 (2016): 74-82. https://doi.org/10.3892/ijmm.2015.2394
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