학술논문

Ultraviolet B-induced Otx2 expression in lens epithelial cells promotes epithelial–mesenchymal transition
Document Type
article
Source
Biology Open, Vol 8, Iss 2 (2019)
Subject
Cataract
UV irradiation
Otx2
Epithelial–mesenchymal transition (EMT)
Science
Biology (General)
QH301-705.5
Language
English
ISSN
2046-6390
Abstract
Ultraviolet (UV) radiation of eyes is a major risk factor for cataractogenesis, although the molecular mechanisms underlying this process remain poorly understood and genes that are affected by UV radiation have not been fully identified. In this study, we examined the UV-related gene regulation in lens epithelial cells (LECs) of mouse eyes and investigated the molecular mechanisms of UV-triggered cataractogenesis. Forty-one genes were significantly upregulated in LECs following UVB exposure in vivo in two independent experiments. Among these, Otx2 was strongly upregulated in LECs, suggesting that it may act as an upstream regulator of UVB-induced changes in gene expression. Accordingly, Otx2 overexpression in LECs in vitro induced morphological changes in cell shapes. Epithelial–mesenchymal transition (EMT)-related molecules, such as TGFβ2, αSMA and fibronectin were upregulated in Otx2-overexpressing LECs, concomitant with suppression of lens fiber cell marker genes, such as CRYAA and DNASEIIB. In vitro experiments suggested that UVB upregulated Otx2 through hydrogen peroxide generation. Aberrant upregulation of Otx2 in LECs following UV irradiation induces the EMT and alteration of the lens cell characteristics, likely contributing to cataractogenesis.