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International Journal of Molecular Medicine
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June-2014 Volume 33 Issue 6

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Article

ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells

  • Authors:
    • Xiaoyun Chen
    • Shaobi Ye
    • Wei Xiao
    • Wencong Wang
    • Lixia Luo
    • Yizhi Liu
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China
  • Pages: 1664-1670
    |
    Published online on: April 4, 2014
       https://doi.org/10.3892/ijmm.2014.1723
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Abstract

Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is the major pathological mechanism in anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), which are important causes of visual impairment. Extracellular signal-regulated kinase (ERK)1/2 pathway has been reported to play a major role in carcinogenesis, cancer metastasis and various fibrotic diseases. We hypothesized that ERK1/2 signaling can cross-interact with canonical transforming growth factor β (TGFβ)/Smad signaling and the Notch pathway, which subsequently contributes to LECs EMT. In this study, we demonstrated that ERK1/2 signaling was activated in TGFβ2‑induced EMT in human LECs, whereas the blockade of TGFβ2/Smad2/3 signaling with SB431542 did not inhibit the activation of ERK1/2 induced by TGFβ2. In addition, inactivation of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor, U0126, completely prevented the TGFβ2-induced upregulation of α-SMA, collagen type I, collagen type IV and fibronectin. We also demonstrated that inactivation of ERK1/2 signaling inhibited canonical TGFβ/Smad signaling, as well as the Jagged/Notch pathway. By contrast, blockade of the Notch pathway by DAPT inhibited the TGFβ2‑induced activation of ERK1/2 pathway in LECs. Thus, results of this study provide evidence for the complex interplay between ERK1/2, TGFβ/Smad, and Jagged/Notch signaling pathways in the regulation of EMT in LECs. Inhibition of the ERK1/2 pathway may therefore have therapeutic value in the prevention and treatment of ASC and PCO.
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Copy and paste a formatted citation
Spandidos Publications style
Chen X, Ye S, Xiao W, Wang W, Luo L and Liu Y: ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells. Int J Mol Med 33: 1664-1670, 2014.
APA
Chen, X., Ye, S., Xiao, W., Wang, W., Luo, L., & Liu, Y. (2014). ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells. International Journal of Molecular Medicine, 33, 1664-1670. https://doi.org/10.3892/ijmm.2014.1723
MLA
Chen, X., Ye, S., Xiao, W., Wang, W., Luo, L., Liu, Y."ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells". International Journal of Molecular Medicine 33.6 (2014): 1664-1670.
Chicago
Chen, X., Ye, S., Xiao, W., Wang, W., Luo, L., Liu, Y."ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells". International Journal of Molecular Medicine 33, no. 6 (2014): 1664-1670. https://doi.org/10.3892/ijmm.2014.1723
Copy and paste a formatted citation
x
Spandidos Publications style
Chen X, Ye S, Xiao W, Wang W, Luo L and Liu Y: ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells. Int J Mol Med 33: 1664-1670, 2014.
APA
Chen, X., Ye, S., Xiao, W., Wang, W., Luo, L., & Liu, Y. (2014). ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells. International Journal of Molecular Medicine, 33, 1664-1670. https://doi.org/10.3892/ijmm.2014.1723
MLA
Chen, X., Ye, S., Xiao, W., Wang, W., Luo, L., Liu, Y."ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells". International Journal of Molecular Medicine 33.6 (2014): 1664-1670.
Chicago
Chen, X., Ye, S., Xiao, W., Wang, W., Luo, L., Liu, Y."ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells". International Journal of Molecular Medicine 33, no. 6 (2014): 1664-1670. https://doi.org/10.3892/ijmm.2014.1723
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