AGE-RAGE interaction in the TGFß2-mediated epithelial to mesenchymal transition of human lens epithelial cells.
Glycoconj J
; 33(4): 631-43, 2016 08.
Article
in En
| MEDLINE
| ID: mdl-27263094
ABSTRACT
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 TGFß2-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 TGFß2-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 TGFß2. RAGE overexpression significantly enhanced the TGFß2-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 TGFß2-mediated EMT response. This was accompanied by a reduction in TGFß2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFß2-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycation End Products, Advanced
/
Epithelial Cells
/
Transforming Growth Factor beta2
/
Epithelial-Mesenchymal Transition
/
Receptor for Advanced Glycation End Products
/
Lens, Crystalline
Limits:
Humans
Language:
En
Journal:
Glycoconj J
Journal subject:
BIOQUIMICA
/
METABOLISMO
Year:
2016
Type:
Article
Affiliation country:
United States