Open AccessAGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis
Author(s) -
Raghavan Cibin T.,
Smuda Mareen,
Smith Andrew J. O.,
Howell Scott,
Smith Dawn G.,
Singh Annapurna,
Gupta Pankaj,
Glomb Marcus A.,
Wormstone Ian Michael,
Nagaraj Ram H.
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12450
Subject(s) - capsule , lens (geology) , biology , glycation , epithelial–mesenchymal transition , downregulation and upregulation , basement membrane , fibrosis , cataracts , microbiology and biotechnology , epithelium , immunology , endocrinology , medicine , diabetes mellitus , biochemistry , gene , genetics , paleontology , botany
Summary Proteins in basement membrane ( BM ) are long‐lived and accumulate chemical modifications during aging; advanced glycation endproduct ( AGE ) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial‐to‐mesenchymal transition ( EMT ) of lens epithelial cells. EMT occurs during posterior capsule opacification ( PCO ), also known as secondary cataract formation. We found age‐dependent increases in several AGE s and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC ‐ MS / MS . The TGF β2‐mediated upregulation of the mRNA levels (by qPCR ) of EMT ‐associated proteins was significantly enhanced in cells cultured on AGE ‐modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGF β1. In the human capsular bag model of PCO , the AGE content of the capsule proteins was correlated with the synthesis of TGF β2‐mediated α‐smooth muscle actin (α SMA ). Taken together, our data imply that AGE s in the lens capsule promote the TGF β2‐mediated fibrosis of lens epithelial cells during PCO and suggest that AGE s in BM s could have a broader role in aging and diabetes‐associated fibrosis.