July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The epigenetic signaling pathway EZH2-H3K27me3 mediates AKT kinase controls of Epithelial-Mesenchymal Transition of Lens Epithelial Cells
Author Affiliations & Notes
  • LAN ZHANG
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jie Xie
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
    Hunan Normal Univ, ChangSha, China
  • Yuan Xiao
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
    Hunan Normal Univ, ChangSha, China
  • Zhigang Chen
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jiawen Xiang
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
    Hunan Normal Univ, ChangSha, China
  • Yizhi Liu
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • David Wan-Cheng Li
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Footnotes
    Commercial Relationships   LAN ZHANG, None; Jie Xie, None; Yuan Xiao, None; Zhigang Chen, None; Jiawen Xiang, None; Yizhi Liu, None; David Wan-Cheng Li, None
  • Footnotes
    Support  National Natural Science Foundation of China, 81570824, 81770910, 81500738, 81500707, and 81700821
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2079. doi:
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      LAN ZHANG, Jie Xie, Yuan Xiao, Zhigang Chen, Jiawen Xiang, Yizhi Liu, David Wan-Cheng Li; The epigenetic signaling pathway EZH2-H3K27me3 mediates AKT kinase controls of Epithelial-Mesenchymal Transition of Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2079.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Posterior capsular opacification is the most common complication after cataract surgery, causing vision impairment. Epithelial-mesenchymal transition (EMT) of the residual lens epithelial cells in the lens capsular bag is a major pathologic change during the development of PCO. Transforming growth factor β (TGFβ) is the prominent factor in ocular aqueous humor driving EMT. A few studies have revealed the correlation between AKT kinase activation and TGFβ-induced EMT of LECs, however, the underlying regulatory mechanisms remain largely unknown. In the present study, we first established the expression profiles of AKT kinase and EZH2 in postnatal mouse lens tissue, and found that either AKT1 kinase or AKT2 kinase inhibition led to impaired mesenchymal gene activation in human and rabbit lens epithelial cells. AKT1 kinase or AKT2 kinase knockdown has similar effect in human lens epithelial cells. We concluded that that AKT kinase participates in the regulation of EMT maker gene expression. Finally, we found that EZH2 S21 phosphorylation by AKT kinase controlled H3K27me3 dynamics, which accounts for the mesenchymal gene activaiton in lens epithelium cells. Sum up, we identified epigenetic signaling pathway EZH2-H3K27me3 mediates AKT kinase controls of EMT of lens epithelial cells.

Methods : Quantitative Real-Time PCR(qRT-PCR), western blot analysis and immuoflurorescence were used to analyze EMT gene expression

Results :
Results: AKT and EZH2 are differentially expressed and phosphorylated in mouse lens and lens epithelium during postnatal development stages. Inhibition of AKT kinase and knockdown of AKT1 or AKT2 leads to attenuated TGFβ1 induced-mesenchymal gene up-regulation in lens epithelial cells, Knockdown of AKT1 or AKT2 mitigates enhanced EZH2 phosphorylation level and dampen the global decrease of H3K27me3. And the overexpression of EZH2 S21 phosphorylation mutant in HLE cells affect TGFβ-induced gene activation of SNAIL1 and FN1.

Conclusions :
AKT1 and AKT2 participate in TGFβ-induced mesenchymal gene activation in in lens epithelial cells, and EZH2 is an important AKT kinase substrate modulating H3K27me3 during TGFβ-induced EMT, and EZH2 S21 phosphorylation is critical for the transcriptional regulation of mesenchymal gene activation.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 


A working model for AKT kinase transcriptionally regulate TGFβ signaling pathway through EZH2-H3K27me3 axis. .


A working model for AKT kinase transcriptionally regulate TGFβ signaling pathway through EZH2-H3K27me3 axis. .

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