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AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens

Purpose: Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cata...

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Autores principales: Wu, Tsung-Tien, Chen, Ying-Ying, Chang, Hui-Yu, Kung, Ya-Hsin, Tseng, Ching-Jiunn, Cheng, Pei-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222180/
https://www.ncbi.nlm.nih.gov/pubmed/32218152
http://dx.doi.org/10.3390/antiox9040273
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author Wu, Tsung-Tien
Chen, Ying-Ying
Chang, Hui-Yu
Kung, Ya-Hsin
Tseng, Ching-Jiunn
Cheng, Pei-Wen
author_facet Wu, Tsung-Tien
Chen, Ying-Ying
Chang, Hui-Yu
Kung, Ya-Hsin
Tseng, Ching-Jiunn
Cheng, Pei-Wen
author_sort Wu, Tsung-Tien
collection PubMed
description Purpose: Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cataracts, but it is unclear whether the prevalence of diabetic cataracts is related to epithelial–mesenchymal transition (EMT) in lens epithelial cells. This study aimed to analyze the role of EMT in cataract formation of DM patients. Methods: Immunofluorescence and immunohistochemistry assays were used to estimate AKR1B1, RAGE, AMPK, and EMT levels in epithelial human lens of DM or non-DM cataracts. Results: Immunohistochemical staining demonstrated that pathologic phases and N-cadherin expression levels were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Immunofluorescent staining showed that AKR1B1 and RAGE were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Interestingly, acetyl superoxide dismutase 2 (AcSOD2) levels were significantly higher in DM patients’ lens epithelial cells (LECs), whereas AMPKT172 phosphorylation was significantly increased in non-DM patients. This indicates that AMPKT172 might be related to superoxide reduction and diabetic cataract formation. Conclusions: Our results suggest that AKR1B1 overexpression can decrease AMPK activation, thereby increasing AcSOD2 and RAGE-induced EMT in epithelial human lens of DM cataracts. These novel findings suggest that AKR inhibitors may be candidates for the pharmacological prevention of cataracts in patients with DM.
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spelling pubmed-72221802020-05-28 AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens Wu, Tsung-Tien Chen, Ying-Ying Chang, Hui-Yu Kung, Ya-Hsin Tseng, Ching-Jiunn Cheng, Pei-Wen Antioxidants (Basel) Article Purpose: Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cataracts, but it is unclear whether the prevalence of diabetic cataracts is related to epithelial–mesenchymal transition (EMT) in lens epithelial cells. This study aimed to analyze the role of EMT in cataract formation of DM patients. Methods: Immunofluorescence and immunohistochemistry assays were used to estimate AKR1B1, RAGE, AMPK, and EMT levels in epithelial human lens of DM or non-DM cataracts. Results: Immunohistochemical staining demonstrated that pathologic phases and N-cadherin expression levels were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Immunofluorescent staining showed that AKR1B1 and RAGE were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Interestingly, acetyl superoxide dismutase 2 (AcSOD2) levels were significantly higher in DM patients’ lens epithelial cells (LECs), whereas AMPKT172 phosphorylation was significantly increased in non-DM patients. This indicates that AMPKT172 might be related to superoxide reduction and diabetic cataract formation. Conclusions: Our results suggest that AKR1B1 overexpression can decrease AMPK activation, thereby increasing AcSOD2 and RAGE-induced EMT in epithelial human lens of DM cataracts. These novel findings suggest that AKR inhibitors may be candidates for the pharmacological prevention of cataracts in patients with DM. MDPI 2020-03-25 /pmc/articles/PMC7222180/ /pubmed/32218152 http://dx.doi.org/10.3390/antiox9040273 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Tsung-Tien
Chen, Ying-Ying
Chang, Hui-Yu
Kung, Ya-Hsin
Tseng, Ching-Jiunn
Cheng, Pei-Wen
AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens
title AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens
title_full AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens
title_fullStr AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens
title_full_unstemmed AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens
title_short AKR1B1-Induced Epithelial–Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens
title_sort akr1b1-induced epithelial–mesenchymal transition mediated by rage-oxidative stress in diabetic cataract lens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222180/
https://www.ncbi.nlm.nih.gov/pubmed/32218152
http://dx.doi.org/10.3390/antiox9040273
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