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Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages

Advanced glycation endproducts (AGEs) have been confirmed to play a causative role in the development of diabetic nephropathy (DN). In this study, we revealed that AGE-induced kidney injury with characteristic patterns in different stages and moesin phosphorylation plays a role in these processes. I...

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Autores principales: Huang, Xiaoxia, Li, Bingyu, Hu, Jiaqing, Liu, Zhuanhua, Li, Dongping, Chen, Zhenfeng, Huang, Hang, Chen, Yanjia, Guo, Xiaohua, Cui, Yun, Huang, Qiaobing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500449/
https://www.ncbi.nlm.nih.gov/pubmed/36160865
http://dx.doi.org/10.3389/fphys.2022.977247
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author Huang, Xiaoxia
Li, Bingyu
Hu, Jiaqing
Liu, Zhuanhua
Li, Dongping
Chen, Zhenfeng
Huang, Hang
Chen, Yanjia
Guo, Xiaohua
Cui, Yun
Huang, Qiaobing
author_facet Huang, Xiaoxia
Li, Bingyu
Hu, Jiaqing
Liu, Zhuanhua
Li, Dongping
Chen, Zhenfeng
Huang, Hang
Chen, Yanjia
Guo, Xiaohua
Cui, Yun
Huang, Qiaobing
author_sort Huang, Xiaoxia
collection PubMed
description Advanced glycation endproducts (AGEs) have been confirmed to play a causative role in the development of diabetic nephropathy (DN). In this study, we revealed that AGE-induced kidney injury with characteristic patterns in different stages and moesin phosphorylation plays a role in these processes. In WT mice treated with AGE-modified bovine serum albumin (AGE-BSA), distinct abnormal angiogenesis in Bowman’s capsule of the kidney emerged early after 1 m under AGE-BSA stimulation, while these neovessels became rare after 6 m. AGE-BSA also induced glomerular hypertrophy and mesangial expansion at 1 m but glomerular atrophy and fibrosis at 6 m. Electron microscopy imaging demonstrated the damage of foot process integrity in podocytes and the uneven thickening of the glomerular basement membrane in the AGE-BSA-treated group, which was more significant after 6 m of AGE-BSA treatment than 1 m. The kidney dysfunction appeared along with these AGE-induced morphological changes. However, these AGE-BSA-induced pathological changes were significantly attenuated in RAGE-knockout mice. Moreover, moesin phosphorylation was accompanied by AGE-BSA-induced alterations and moesin deficiency in mice attenuated by AGE-BSA-induced fibrosis. The investigation on glomerular endothelial cells (GECs) also confirmed that the phosphorylation of moesin T558 is critical in AGE-induced tube formation. Overall, this study suggests that AGEs mediate kidney injury with characteristic patterns by binding with RAGE and inducing moesin phosphorylation.
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spelling pubmed-95004492022-09-24 Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages Huang, Xiaoxia Li, Bingyu Hu, Jiaqing Liu, Zhuanhua Li, Dongping Chen, Zhenfeng Huang, Hang Chen, Yanjia Guo, Xiaohua Cui, Yun Huang, Qiaobing Front Physiol Physiology Advanced glycation endproducts (AGEs) have been confirmed to play a causative role in the development of diabetic nephropathy (DN). In this study, we revealed that AGE-induced kidney injury with characteristic patterns in different stages and moesin phosphorylation plays a role in these processes. In WT mice treated with AGE-modified bovine serum albumin (AGE-BSA), distinct abnormal angiogenesis in Bowman’s capsule of the kidney emerged early after 1 m under AGE-BSA stimulation, while these neovessels became rare after 6 m. AGE-BSA also induced glomerular hypertrophy and mesangial expansion at 1 m but glomerular atrophy and fibrosis at 6 m. Electron microscopy imaging demonstrated the damage of foot process integrity in podocytes and the uneven thickening of the glomerular basement membrane in the AGE-BSA-treated group, which was more significant after 6 m of AGE-BSA treatment than 1 m. The kidney dysfunction appeared along with these AGE-induced morphological changes. However, these AGE-BSA-induced pathological changes were significantly attenuated in RAGE-knockout mice. Moreover, moesin phosphorylation was accompanied by AGE-BSA-induced alterations and moesin deficiency in mice attenuated by AGE-BSA-induced fibrosis. The investigation on glomerular endothelial cells (GECs) also confirmed that the phosphorylation of moesin T558 is critical in AGE-induced tube formation. Overall, this study suggests that AGEs mediate kidney injury with characteristic patterns by binding with RAGE and inducing moesin phosphorylation. Frontiers Media S.A. 2022-09-09 /pmc/articles/PMC9500449/ /pubmed/36160865 http://dx.doi.org/10.3389/fphys.2022.977247 Text en Copyright © 2022 Huang, Li, Hu, Liu, Li, Chen, Huang, Chen, Guo, Cui and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Huang, Xiaoxia
Li, Bingyu
Hu, Jiaqing
Liu, Zhuanhua
Li, Dongping
Chen, Zhenfeng
Huang, Hang
Chen, Yanjia
Guo, Xiaohua
Cui, Yun
Huang, Qiaobing
Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
title Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
title_full Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
title_fullStr Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
title_full_unstemmed Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
title_short Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
title_sort advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500449/
https://www.ncbi.nlm.nih.gov/pubmed/36160865
http://dx.doi.org/10.3389/fphys.2022.977247
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