JNK1/β-catenin axis regulates H₂O₂-induced epithelial-to-mesenchymal transition in human lens epithelial cells

Epithelial-mesenchymal transition (EMT) is the main cause of fibrotic cataracts. Oxidative stress was recently shown to trigger epithelial-mesenchymal transition in human lens epithelial cells (hLECs). However, the underlying mechanism is not fully understood. Here we reported that exposure to low doses (100 μM) of H₂O₂ led to EMT in hLECs, as indicated by simultaneous down-regulated of E-cadherin and ZO-1, and up-regulated of alpha smooth muscle actin (α-SMA). H₂O₂-induced EMT was accompanied by accumulation of phosphorylated JNK1. In contrast, knockdown of JNK1 via siRNA reversed H₂O₂-induced EMT. Of interest, in human lens capsules of anterior subcapsule cataracts, the expressions of JNK1, as well as β-catenin and its downstream effectors cyclin D and c-Myc, were augmented compared to that in normal lens capsules. Mechanistically, activated JNK1 dislodged β-catenin from the cell membrane, which subsequently translocated to the nuclei and triggered transcription of its effectors. Nuclei β-catenin, cyclin D and c-Myc were accumulated in H₂O₂-induced EMT and JNK1 depletion abrogated these trend in hLECs. In conclusion, our data suggest that JNK1 is essential for H₂O₂-induced EMT in hLECs via mediating the translocation of β-catenin.