AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells

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 TGFβ2-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 TGFβ2-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 TGFβ2. RAGE overexpression significantly enhanced the TGFβ2-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 TGFβ2-mediated EMT response. This was accompanied by a reduction in TGFβ2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFβ2-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.

Influence of aldose reductase on epithelial-to-mesenchymal transition signaling in lens epithelial cells

“…In an potentially related area, it is interesting to note that fructose, the end product of AR polyol pathway, has been demonstrated to form advanced glycated end-products (AGEs) much faster than glucose [35]. Raghavan and colleagues recently reported that AGEs in lens capsule enhance EMT of LECs under TGF-β2 treatment [36, 37]. Accordingly, AR-induced AGEs production might be another stimulus for PCO development following cataract surgery.…”

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

“…The fetal human lens epithelial cell line (FHL124) was kindly provided by Prof. Michael Wormstone (School of Biological Sciences, University of East Anglia, UK, originally from Prof. John Reddan, Oakland University, MI). FHL124 cells were cultured as previously described [38] and treated with aspirin (Sigma-Aldrich, St. Louis, MO, Cat# A5376) at 2 mM for 24 h and then cotreated with 10 ng/ml TGFβ2 (Peprotech, Inc., Rocky Hill, NJ, Cat# 100-35B,10 ng/ml) for the additional indicated times. The MTT assay was used to determine the cytotoxicity of aspirin or cell proliferation.…”

A preliminary study on the formation pathways of glycated phosphatidylethanolamine of food rich in phospholipid during the heat-processing

“…The Maillard reaction of protein glycation and its involvement in the pathogenesis of diabetic complications has been thoroughly investigated. 1,2 In addition to protein glycation, amino lipids, such as phosphatidylethanolamine (PE) and phosphatidylserine (PS), could be involved in the Maillard reaction with reducing sugars, due to their free amino group. 3,4 In vivo studies demonstrated that membrane phospholipids such as PE were abnormally glycated under hyperglycemic conditions, which led to destruction of cellular integrity and functionality.…”