The mechanism of long-term low-dose asymmetric dimethylarginine inducing transforming growth factor-β expression in endothelial cells

  • Authors:
    • Yiduo Feng
    • Dongliang Zhang
    • Yu Zhang
    • Qidong Zhang
    • Wenhu Liu
  • View Affiliations

  • Published online on: November 20, 2012     https://doi.org/10.3892/ijmm.2012.1190
  • Pages: 67-74
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Abstract

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, accumulates in plasma during chronic kidney disease (CKD). High plasma levels of ADMA can increase transforming growth factor-β (TGF-β) expression, related to renal fibrosis, but the precise molecular mechanism is not explicit. The present study was designed to determine the mechanism through which long-term low-dose ADMA induces TGF-β expression in endothelial cells and to investigate the molecular mechanism of its action. Human umbilical vein endothelial cells (HUVECs) were exposed to low-dose ADMA (5 and 10 µmol/l) for 7 passages and TGF-β expression was determined. Human renal glomerular endothelial cells (HRGECs) were exposed to high-dose ADMA (100 µmol/l) which were used to clarify the molecular mechanism. The results showed that long-term low-dose ADMA (5 and 10 µmol/l) increases TGF-β production in both mRNA and protein levels in HUVECs in a time-dependent manner. We confirmed that exogenous ADMA (100 µmol/l) significantly enhanced stress fiber formation in HRGECs and upregulated TGF-β expression. Such effects of ADMA in HRGECs were inhibited by pre-treatment with actin depolymerizing agent, actin stabilizing agent, p38 MAPK inhibitor and NADPH oxidase inhibitor. In addition, we demonstrated that ADMA (100 µmol/l) significantly activated nuclear factor-κB (NF-κB) in HRGECs, which was markedly attenuated by actin depolymerizing agent, actin stabilizing agent, p38 MAPK inhibitor and NADPH oxidase inhibitor. In brief, the present study demonstrated that long-term low-dose ADMA induces TGF-β expression in endothelial cells at both the gene and protein levels. The actin cytoskeleton may be involved in modulation of ADMA-induced NF-κB activation and the ensuing TGF-β expression in HRGECs.
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January 2013
Volume 31 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Feng Y, Zhang D, Zhang Y, Zhang Q and Liu W: The mechanism of long-term low-dose asymmetric dimethylarginine inducing transforming growth factor-β expression in endothelial cells. Int J Mol Med 31: 67-74, 2013
APA
Feng, Y., Zhang, D., Zhang, Y., Zhang, Q., & Liu, W. (2013). The mechanism of long-term low-dose asymmetric dimethylarginine inducing transforming growth factor-β expression in endothelial cells. International Journal of Molecular Medicine, 31, 67-74. https://doi.org/10.3892/ijmm.2012.1190
MLA
Feng, Y., Zhang, D., Zhang, Y., Zhang, Q., Liu, W."The mechanism of long-term low-dose asymmetric dimethylarginine inducing transforming growth factor-β expression in endothelial cells". International Journal of Molecular Medicine 31.1 (2013): 67-74.
Chicago
Feng, Y., Zhang, D., Zhang, Y., Zhang, Q., Liu, W."The mechanism of long-term low-dose asymmetric dimethylarginine inducing transforming growth factor-β expression in endothelial cells". International Journal of Molecular Medicine 31, no. 1 (2013): 67-74. https://doi.org/10.3892/ijmm.2012.1190