期刊
GLYCOCONJUGATE JOURNAL
卷 33, 期 4, 页码 631-643出版社
SPRINGER
DOI: 10.1007/s10719-016-9686-y
关键词
Posterior capsule opacification; Basement membrane; Epithelial to mesenchymal transition; AGEs; EN-RAGE; RAGE
资金
- National Institutes of Health [EY022061, EY023286]
Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGF beta 2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGF beta 2-mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGF beta 2. RAGE overexpression significantly enhanced the TGF beta 2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGF beta 2-mediated EMT response. This was accompanied by a reduction in TGF beta 2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGF beta 2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age-associated fibrosis.
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