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Advanced glycation end products regulate the receptor of AGEs epigenetically

Advanced glycation end-products (AGEs) can boost their receptor of AGE (RAGE) expression through the downstream signaling pathway to facilitate AGE–RAGE interaction. In this regulation process, the primary signaling pathways are NF-κB and STAT3. However, the inhibition of these transcription factors...

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Autores principales: Wu, Xiaoqing, Shi, Xuanren, Chen, Xiaoyong, Yin, Zhanhai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971228/
https://www.ncbi.nlm.nih.gov/pubmed/36866277
http://dx.doi.org/10.3389/fcell.2023.1062229
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author Wu, Xiaoqing
Shi, Xuanren
Chen, Xiaoyong
Yin, Zhanhai
author_facet Wu, Xiaoqing
Shi, Xuanren
Chen, Xiaoyong
Yin, Zhanhai
author_sort Wu, Xiaoqing
collection PubMed
description Advanced glycation end-products (AGEs) can boost their receptor of AGE (RAGE) expression through the downstream signaling pathway to facilitate AGE–RAGE interaction. In this regulation process, the primary signaling pathways are NF-κB and STAT3. However, the inhibition of these transcription factors cannot completely block the upregulation of RAGE, which indicates AGEs may also impact RAGE expression via other pathways. In this study, we revealed that AGEs can exhibit epigenetic impacts on RAGE expression. Here, we used carboxymethyl-lysine (CML) and carboxyethyl-lysine (CEL) to treat liver cells and discovered that AGEs can promote the demethylation of the RAGE promoter region. To verify this epigenetic modification, we employed dCAS9-DNMT3a with sgRNA to specifically modify the RAGE promoter region against the effect of carboxymethyl-lysine and carboxyethyl-lysine. The elevated RAGE expressions were partially repressed after AGE-induced hypomethylation statuses were reversed. Additionally, TET1 were also upregulated in AGE-treated cells, indicating AGEs may epigenetically modulate RAGE through the elevating TET1 level.
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spelling pubmed-99712282023-03-01 Advanced glycation end products regulate the receptor of AGEs epigenetically Wu, Xiaoqing Shi, Xuanren Chen, Xiaoyong Yin, Zhanhai Front Cell Dev Biol Cell and Developmental Biology Advanced glycation end-products (AGEs) can boost their receptor of AGE (RAGE) expression through the downstream signaling pathway to facilitate AGE–RAGE interaction. In this regulation process, the primary signaling pathways are NF-κB and STAT3. However, the inhibition of these transcription factors cannot completely block the upregulation of RAGE, which indicates AGEs may also impact RAGE expression via other pathways. In this study, we revealed that AGEs can exhibit epigenetic impacts on RAGE expression. Here, we used carboxymethyl-lysine (CML) and carboxyethyl-lysine (CEL) to treat liver cells and discovered that AGEs can promote the demethylation of the RAGE promoter region. To verify this epigenetic modification, we employed dCAS9-DNMT3a with sgRNA to specifically modify the RAGE promoter region against the effect of carboxymethyl-lysine and carboxyethyl-lysine. The elevated RAGE expressions were partially repressed after AGE-induced hypomethylation statuses were reversed. Additionally, TET1 were also upregulated in AGE-treated cells, indicating AGEs may epigenetically modulate RAGE through the elevating TET1 level. Frontiers Media S.A. 2023-02-14 /pmc/articles/PMC9971228/ /pubmed/36866277 http://dx.doi.org/10.3389/fcell.2023.1062229 Text en Copyright © 2023 Wu, Shi, Chen and Yin. 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 Cell and Developmental Biology
Wu, Xiaoqing
Shi, Xuanren
Chen, Xiaoyong
Yin, Zhanhai
Advanced glycation end products regulate the receptor of AGEs epigenetically
title Advanced glycation end products regulate the receptor of AGEs epigenetically
title_full Advanced glycation end products regulate the receptor of AGEs epigenetically
title_fullStr Advanced glycation end products regulate the receptor of AGEs epigenetically
title_full_unstemmed Advanced glycation end products regulate the receptor of AGEs epigenetically
title_short Advanced glycation end products regulate the receptor of AGEs epigenetically
title_sort advanced glycation end products regulate the receptor of ages epigenetically
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971228/
https://www.ncbi.nlm.nih.gov/pubmed/36866277
http://dx.doi.org/10.3389/fcell.2023.1062229
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