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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9500449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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