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Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone met...

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Autores principales: Martinez-Moreno, Julio M., Fontecha-Barriuso, Miguel, Martin-Sanchez, Diego, Guerrero-Mauvecin, Juan, Goma-Garces, Elena, Fernandez-Fernandez, Beatriz, Carriazo, Sol, Sanchez-Niño, Maria D., Ramos, Adrian M., Ruiz-Ortega, Marta, Ortiz, Alberto, Sanz, Ana B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312774/
https://www.ncbi.nlm.nih.gov/pubmed/32526941
http://dx.doi.org/10.3390/ijms21114113
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author Martinez-Moreno, Julio M.
Fontecha-Barriuso, Miguel
Martin-Sanchez, Diego
Guerrero-Mauvecin, Juan
Goma-Garces, Elena
Fernandez-Fernandez, Beatriz
Carriazo, Sol
Sanchez-Niño, Maria D.
Ramos, Adrian M.
Ruiz-Ortega, Marta
Ortiz, Alberto
Sanz, Ana B.
author_facet Martinez-Moreno, Julio M.
Fontecha-Barriuso, Miguel
Martin-Sanchez, Diego
Guerrero-Mauvecin, Juan
Goma-Garces, Elena
Fernandez-Fernandez, Beatriz
Carriazo, Sol
Sanchez-Niño, Maria D.
Ramos, Adrian M.
Ruiz-Ortega, Marta
Ortiz, Alberto
Sanz, Ana B.
author_sort Martinez-Moreno, Julio M.
collection PubMed
description Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone methylation, acetylation and crotonylation—in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.
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spelling pubmed-73127742020-06-26 Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease Martinez-Moreno, Julio M. Fontecha-Barriuso, Miguel Martin-Sanchez, Diego Guerrero-Mauvecin, Juan Goma-Garces, Elena Fernandez-Fernandez, Beatriz Carriazo, Sol Sanchez-Niño, Maria D. Ramos, Adrian M. Ruiz-Ortega, Marta Ortiz, Alberto Sanz, Ana B. Int J Mol Sci Review Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone methylation, acetylation and crotonylation—in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies. MDPI 2020-06-09 /pmc/articles/PMC7312774/ /pubmed/32526941 http://dx.doi.org/10.3390/ijms21114113 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martinez-Moreno, Julio M.
Fontecha-Barriuso, Miguel
Martin-Sanchez, Diego
Guerrero-Mauvecin, Juan
Goma-Garces, Elena
Fernandez-Fernandez, Beatriz
Carriazo, Sol
Sanchez-Niño, Maria D.
Ramos, Adrian M.
Ruiz-Ortega, Marta
Ortiz, Alberto
Sanz, Ana B.
Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
title Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
title_full Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
title_fullStr Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
title_full_unstemmed Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
title_short Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease
title_sort epigenetic modifiers as potential therapeutic targets in diabetic kidney disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312774/
https://www.ncbi.nlm.nih.gov/pubmed/32526941
http://dx.doi.org/10.3390/ijms21114113
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