期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 476, 期 3, 页码 1631-1642出版社
SPRINGER
DOI: 10.1007/s11010-020-04034-9
关键词
Lens epithelial cells; Epithelial-mesenchymal transition; Wnt/beta-catenin pathway; TGF-beta/Smad pathway; Oxidative stress
类别
资金
- National Natural Science Foundation of China [81873674]
The study demonstrates that both TGF-beta/Smad and canonical Wnt/beta-catenin pathways play a significant role in regulating epithelial-mesenchymal transformation of lens epithelial cells but might be in a different stage.
The epithelial-mesenchymal transition (EMT) plays a significant role in fibrosis and migration of lens epithelial cells (LECs), and eventually induces posterior capsule opacification (PCO). In the past, it was generally believed that the TGF-beta/Smad pathway regulates lens EMT. A recent study found that attenuated glutathione level promotes LECs EMT via the Wnt/beta-catenin pathway, which suggests a more complex pathogenesis of PCO. To test the hypothesis, we used the mouse cataract surgery PCO model and tested both canonical Wnt/beta-catenin and TGF-beta/Smad signaling pathways. The results showed that both TGF-beta/Smad and Wnt/beta-catenin pathways were activated during the lens capsule fibrosis. Compared with the freshly isolated posterior capsule, the expression level of phosphorylated Smad2 was highest at day3 and then slightly decreased, but the expression level of Wnt10a gradually increased from day0 to day7. It shows that these two pathways are involved in the lens epithelium's fibrotic process and may play different roles in different periods. Subsequently, we established oxidative stress-induced EMT model in primary porcine lens epithelial cells and found that both the TGF-beta/Smad and Wnt/beta-catenin pathways were activated. Further study suggests that block Wnt/beta-catenin pathway using XAV939 alone or block TGF-beta/Smad pathway using LY2109761 could partially block pLECs fibrosis, but blocking Wnt/beta-catenin and TGF-beta/Smad pathway using combined XAV939 and LY2109761 could completely block pLECs fibrosis. In conclusion, this study demonstrates that both TGF-beta/Smad and canonical Wnt/beta-catenin pathways play a significant role in regulating epithelial-mesenchymal transformation of lens epithelial cells but might be in a different stage.
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