JNK1/ß-catenin axis regulates H2O2-induced epithelial-to-mesenchymal transition in human lens epithelial cells.
Biochem Biophys Res Commun
; 511(2): 336-342, 2019 04 02.
Article
in En
| MEDLINE
| ID: mdl-30791985
ABSTRACT
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⯵M) 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 ß-catenin and its downstream effectors cyclin D and c-Myc, were augmented compared to that in normal lens capsules. Mechanistically, activated JNK1 dislodged ß-catenin from the cell membrane, which subsequently translocated to the nuclei and triggered transcription of its effectors. Nuclei ß-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 ß-catenin.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Mitogen-Activated Protein Kinase 8
/
Beta Catenin
/
Epithelial-Mesenchymal Transition
/
Hydrogen Peroxide
/
Lens Capsule, Crystalline
Limits:
Adult
/
Humans
/
Middle aged
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2019
Type:
Article