UVB radiation induces human lens epithelial cell migration via NADPH oxidase-mediated generation of reactive oxygen species and up-regulation of matrix metalloproteinases.
Ultraviolet (UV) radiation is one of the important cataract risk factors. The migration of human lens epithelial cells (HLECs) plays a crucial role in the remodeling of lens capsule and cataract formation. The purpose of the present study was to investigate the molecular mechanisms of UV-induced lens cell migration. We found that UVB radiation induces cell migration in cultured human lens epithelial cells. Further, we observed that UVB radiation induces NADPH oxidase activity and ROS generation which are inhibited by NADPH oxidase inhibitor diphenylene iodonium or DPI and antioxidant epigallocatechin gallate (EGCG). In addition, DPI and EGCG also block UVB irradiation-induced MMP-2, and -9 activity and expression and nuclear translocation of NF-kappaB. Collectively, our data suggest that NADPH oxidase may be a major source for the UVB-induced ROS generation, and it plays an essential role in the activation of NF-kappaB, which is involved in the activities of MMP-2 and MMP-9 and cell migration induced by UVB in HELCs. Understanding the cell signaling pathways may constitute potential therapeutic targets in for UVB-induced cataract.
Yao
Jin
J
Eye Hospital, Nanjing Medical University, Nanjing, PR China.
Liu
Yuan
Y
Wang
Xinru
X
Shen
Yi
Y
Yuan
Songtao
S
Wan
Yinsheng
Y
Jiang
Qin
Q
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D019255:NADPH Oxidases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D019255:NADPH Oxidases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9