首页 | 本学科首页   官方微博 | 高级检索  
   检索      


AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis
Authors:Cibin T Raghavan  Mareen Smuda  Andrew J O Smith  Scott Howell  Dawn G Smith  Annapurna Singh  Pankaj Gupta  Marcus A Glomb  Ian Michael Wormstone  Ram H Nagaraj
Institution:1. Department of Ophthalmology & Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA;2. Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA;3. Institute of Chemistry, Martin‐Luther‐University Halle‐Wittenberg, Halle/Saale, Germany;4. School of Biological Sciences, University of East Anglia, Norwich, UK;5. Visual Sciences Research Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA;6. University Hospitals Eye Institute, Cleveland, OH, USA
Abstract: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 AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC‐MS/MS. The TGFβ2‐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 TGFβ1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGFβ2‐mediated α‐smooth muscle actin (αSMA). Taken together, our data imply that AGEs in the lens capsule promote the TGFβ2‐mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes‐associated fibrosis.
Keywords:advanced glycation endproducts  basement membrane  epithelial‐to‐mesenchymal transition  fibrosis  lens epithelial cells  posterior capsular opacification
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号