The Notch pathway mediates the angiotensin II-induced synthesis of extracellular matrix components in podocytes

  • Authors:
    • Min Yao
    • Xiaomei Wang
    • Xiaomeng Wang
    • Tao Zhang
    • Yanqing Chi
    • Feng Gao
  • View Affiliations

  • Published online on: April 22, 2015     https://doi.org/10.3892/ijmm.2015.2193
  • Pages: 294-300
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Abstract

The Notch pathway is known to contribute to the development of glomerular disease. Angiotensin II (Ang II), an important member of the renin-angiotensin system, stimulates the accumulation of extracellular matrix components in glomerular disease; however, the exact mechanisms involved remain to be elucidated. In the present study, we aimed to investigate the effects of the Notch pathway on the synthesis of extracellular matrix components in Ang II-stimulated podocytes. Mouse podocytes were stimulated with Ang II (10-6 mol/l). The activation of the Notch pathway was inhibited by a vector carrying short hairpin RNA (shRNA) targeting Notch1 (sh-Notch1) or by γ-secretase inhibitor (GSI). The protein levels of Notch1, Notch intracellular domain 1 (NICD1), hairy and enhancer of split-1 (Hes1), matrix metalloproteinase (MMP)-2, MMP-9, transforming growth factor-β1 (TGF-β1), type IV collagen and laminin were determined by western blot analysis. The Notch1, Hes1, MMP-2, MMP-9, TGF-β1, type IV collagen and laminin mRNA levels were detected by RT-PCR. The MMP-2 and MMP-9 activity was measured using a cell active fluorescence assay kit. The levels of TGF-β1, type IV collagen and laminin were determined in the culture medium of the podocytes by enzyme-linked immunosorbent assay (ELISA). Our results revealed that Ang II upregulated Notch1, NICD1, Hes1, TGF-β1, type IV collagen and laminin expression and downregulated MMP-2 and MMP-9 expression in the cultured podocytes. The inhibition of the Notch pathway by sh-Notch1 or GSI increased MMP-2 and MMP-9 expression, decreased the TGF-β1 level and suppressed type IV collagen and laminin expression. The inhibition of the Notch pathway by sh-Notch1 or GSI also increased MMP-2 and MMP-9 activity, and decreased TGF-β1 levels, type IV collagen levels and laminin secretion. These findings indicate that the Notch pathway potentially mediates the Ang II-induced synthesis of extracellular matrix components in podocytes through the regulation of MMPs and TGF-β1.
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July-2015
Volume 36 Issue 1

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

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Spandidos Publications style
Yao M, Wang X, Wang X, Zhang T, Chi Y and Gao F: The Notch pathway mediates the angiotensin II-induced synthesis of extracellular matrix components in podocytes. Int J Mol Med 36: 294-300, 2015
APA
Yao, M., Wang, X., Wang, X., Zhang, T., Chi, Y., & Gao, F. (2015). The Notch pathway mediates the angiotensin II-induced synthesis of extracellular matrix components in podocytes. International Journal of Molecular Medicine, 36, 294-300. https://doi.org/10.3892/ijmm.2015.2193
MLA
Yao, M., Wang, X., Wang, X., Zhang, T., Chi, Y., Gao, F."The Notch pathway mediates the angiotensin II-induced synthesis of extracellular matrix components in podocytes". International Journal of Molecular Medicine 36.1 (2015): 294-300.
Chicago
Yao, M., Wang, X., Wang, X., Zhang, T., Chi, Y., Gao, F."The Notch pathway mediates the angiotensin II-induced synthesis of extracellular matrix components in podocytes". International Journal of Molecular Medicine 36, no. 1 (2015): 294-300. https://doi.org/10.3892/ijmm.2015.2193