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Jinyan Li, Yijia Chen, Lixia Luo; JNK1 Regulates Epithelial-to-Mesenchymal Transition via β-catenin Signaling in Human Lens Epithelial Cells Exposed to Hydrogen Peroxide. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1122.
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Oxidative stress was recently shown to trigger epithelial-mesenchymal transition in human lens epithelial cells. Thus, we investigated whether JNK, which responds to oxidative stress, is involved in this phenomenon.
JNK and β-catenin were assessed in clinical samples of anterior subcapsule cataract. Markers of epithelial-mesenchymal transition, JNK, phosphorylated JNK, β-catenin pathways, and TGF-β cascades were quantified by quantitative reverse-transcription PCR and western blotting in human lens epithelial cells exposed to hydrogen peroxide in vitro in the presence or absence of JNK1-interfering RNAs, or small-molecule JNK1 and β-catenin inhibitors.
Both immunofluorescent staining and quantitative reverse-transcription PCR showed that α-SMA and JNK1 were upregulated in opaque plates in anterior subcapsule cataracts, and active β-catenin was observed. On the other hand, human lens epithelial cells underwent epithelial-mesenchymal transition after exposure to low doses of H2O2, as indicated by dynamic changes in gene expression, cell morphology, mobility, and proliferation. We found that besides TGF-β cascades, this process was accompanied by accumulation of both phosphorylated and unphosphorylated JNK1. Knockdown of JNK1 and exposure to the JNK1 inhibitor SP600125 reversed the effects of H2O2 and the subsequent β-catenin signaling, while the β-catenin inhibitor XAV939 did not affect JNK status in response to H2O2.
The data indicate that the JNK1/β-catenin axis links oxidative damage from H2O2 to epithelial-mesenchymal transition in lens epithelial cells. The data also provide new opportunities to prevent formation of subcapsular cataracts.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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