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Advanced glycation end products regulate the receptor of AGEs epigenetically.

ABSTRACT: 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.

SUBMITTER: Wu X

PROVIDER: S-EPMC9971228 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Advanced glycation end products regulate the receptor of AGEs epigenetically.

Wu Xiaoqing X Shi Xuanren X Chen Xiaoyong X Yin Zhanhai Z

Frontiers in cell and developmental biology 20230214

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 <i>via</i> other pathways. In this study, we revealed that AGEs can exhibit epigenetic impacts o ...[more]

PMID: 36866277

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Project description:ContextAdvanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports.Evidence acquisitionEvidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles.ResultsPharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF.ConclusionsDespite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.

Dataset Information

Advanced glycation end products regulate the receptor of AGEs epigenetically.

Publications

Advanced glycation end products regulate the receptor of AGEs epigenetically.

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