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Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases

Epigenetic mechanisms, especially DNA methylation and histone modifications, are dynamic processes that regulate the gene expression transcriptional program in normal and diseased states. The bromodomain and extraterminal (BET) protein family (BRD2, BRD3, BRD4, and BRDT) are epigenetic readers that,...

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Autores principales: Morgado-Pascual, Jose Luis, Rayego-Mateos, Sandra, Tejedor, Lucia, Suarez-Alvarez, Beatriz, Ruiz-Ortega, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857099/
https://www.ncbi.nlm.nih.gov/pubmed/31780938
http://dx.doi.org/10.3389/fphar.2019.01315
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author Morgado-Pascual, Jose Luis
Rayego-Mateos, Sandra
Tejedor, Lucia
Suarez-Alvarez, Beatriz
Ruiz-Ortega, Marta
author_facet Morgado-Pascual, Jose Luis
Rayego-Mateos, Sandra
Tejedor, Lucia
Suarez-Alvarez, Beatriz
Ruiz-Ortega, Marta
author_sort Morgado-Pascual, Jose Luis
collection PubMed
description Epigenetic mechanisms, especially DNA methylation and histone modifications, are dynamic processes that regulate the gene expression transcriptional program in normal and diseased states. The bromodomain and extraterminal (BET) protein family (BRD2, BRD3, BRD4, and BRDT) are epigenetic readers that, via bromodomains, regulate gene transcription by binding to acetylated lysine residues on histones and master transcriptional factors. Experimental data have demonstrated the involvement of some BET proteins in many pathological conditions, including tumor development, infections, autoimmunity, and inflammation. Selective bromodomain inhibitors are epigenetic drugs that block the interaction between BET proteins and acetylated proteins, thus exerting beneficial effects. Recent data have described the beneficial effect of BET inhibition on experimental renal diseases. Emerging evidence underscores the importance of environmental modifications in the origin of pathological features in chronic kidney diseases (CKD). Several cellular processes such as oxidation, metabolic disorders, cytokines, inflammation, or accumulated uremic toxins may induce epigenetic modifications that regulate key processes involved in renal damage and in other pathological conditions observed in CKD patients. Here, we review how targeting bromodomains in BET proteins may regulate essential processes involved in renal diseases and in associated complications found in CKD patients, such as cardiovascular damage, highlighting the potential of epigenetic therapeutic strategies against BET proteins for CKD treatment and associated risks.
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spelling pubmed-68570992019-11-28 Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases Morgado-Pascual, Jose Luis Rayego-Mateos, Sandra Tejedor, Lucia Suarez-Alvarez, Beatriz Ruiz-Ortega, Marta Front Pharmacol Pharmacology Epigenetic mechanisms, especially DNA methylation and histone modifications, are dynamic processes that regulate the gene expression transcriptional program in normal and diseased states. The bromodomain and extraterminal (BET) protein family (BRD2, BRD3, BRD4, and BRDT) are epigenetic readers that, via bromodomains, regulate gene transcription by binding to acetylated lysine residues on histones and master transcriptional factors. Experimental data have demonstrated the involvement of some BET proteins in many pathological conditions, including tumor development, infections, autoimmunity, and inflammation. Selective bromodomain inhibitors are epigenetic drugs that block the interaction between BET proteins and acetylated proteins, thus exerting beneficial effects. Recent data have described the beneficial effect of BET inhibition on experimental renal diseases. Emerging evidence underscores the importance of environmental modifications in the origin of pathological features in chronic kidney diseases (CKD). Several cellular processes such as oxidation, metabolic disorders, cytokines, inflammation, or accumulated uremic toxins may induce epigenetic modifications that regulate key processes involved in renal damage and in other pathological conditions observed in CKD patients. Here, we review how targeting bromodomains in BET proteins may regulate essential processes involved in renal diseases and in associated complications found in CKD patients, such as cardiovascular damage, highlighting the potential of epigenetic therapeutic strategies against BET proteins for CKD treatment and associated risks. Frontiers Media S.A. 2019-11-08 /pmc/articles/PMC6857099/ /pubmed/31780938 http://dx.doi.org/10.3389/fphar.2019.01315 Text en Copyright © 2019 Morgado-Pascual, Rayego-Mateos, Tejedor, Suarez-Alvarez and Ruiz-Ortega http://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 Pharmacology
Morgado-Pascual, Jose Luis
Rayego-Mateos, Sandra
Tejedor, Lucia
Suarez-Alvarez, Beatriz
Ruiz-Ortega, Marta
Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
title Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
title_full Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
title_fullStr Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
title_full_unstemmed Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
title_short Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases
title_sort bromodomain and extraterminal proteins as novel epigenetic targets for renal diseases
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857099/
https://www.ncbi.nlm.nih.gov/pubmed/31780938
http://dx.doi.org/10.3389/fphar.2019.01315
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