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...
| Autores: | , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/694819 |
| Acesso em linha: | http://hdl.handle.net/10486/694819 https://dx.doi.org/10.3390/ijms21114113 |
| Access Level: | acceso abierto |
| Palavra-chave: | Apabetalone BET Chronic kidney disease Crotonylation Diabetes Diabetic kidney disease DNA methylation Epigenetic Farmacia Medicina |
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Epigenetic modifiers as potential therapeutic targets in diabetic kidney diseaseMartinez-Moreno, Julio M.Fontecha-Barriuso, MiguelMartin-Sanchez, DiegoGuerrero-Mauvecin, JuanGoma-Garces, ElenaFernández Fernández, BeatrizCarriazo, SolSánchez Niño, María DoloresRamos, Adrian M.Ruiz Ortega, MartaOrtiz Arduán, AlbertoSanz, Ana BelénApabetaloneBETChronic kidney diseaseCrotonylationDiabetesDiabetic kidney diseaseDNA methylationEpigeneticFarmaciaMedicinaDiabetic 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.This research was funded by FIS/FEDER funds (PI15/00298, CP14/00133, PI16/01900, PI18/01386, PI18/0133, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071), ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD- 3686 CIFRA2-CM. Salary support: ISCIII Miguel Servet to ABS and MDS-N, ISCIII Sara Borrell to JM-MM, REDinREN RD016/0009 to MF-B, and MICIU to JG-M.MDPI, Basel, SMwitzerlandDepartamento de FarmacologíaDepartamento de MedicinaFacultad de MedicinaInstituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)20202020-06-09research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/694819https://dx.doi.org/10.3390/ijms21114113reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6948192026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Epigenetic modifiers as potential therapeutic targets in diabetic kidney disease |
| title |
Epigenetic modifiers as potential therapeutic targets in diabetic kidney disease |
| spellingShingle |
Epigenetic modifiers as potential therapeutic targets in diabetic kidney disease Martinez-Moreno, Julio M. Apabetalone BET Chronic kidney disease Crotonylation Diabetes Diabetic kidney disease DNA methylation Epigenetic Farmacia Medicina |
| title_short |
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_sort |
Epigenetic modifiers as potential therapeutic targets in diabetic kidney disease |
| dc.creator.none.fl_str_mv |
Martinez-Moreno, Julio M. Fontecha-Barriuso, Miguel Martin-Sanchez, Diego Guerrero-Mauvecin, Juan Goma-Garces, Elena Fernández Fernández, Beatriz Carriazo, Sol Sánchez Niño, María Dolores Ramos, Adrian M. Ruiz Ortega, Marta Ortiz Arduán, Alberto Sanz, Ana Belén |
| author |
Martinez-Moreno, Julio M. |
| author_facet |
Martinez-Moreno, Julio M. Fontecha-Barriuso, Miguel Martin-Sanchez, Diego Guerrero-Mauvecin, Juan Goma-Garces, Elena Fernández Fernández, Beatriz Carriazo, Sol Sánchez Niño, María Dolores Ramos, Adrian M. Ruiz Ortega, Marta Ortiz Arduán, Alberto Sanz, Ana Belén |
| author_role |
author |
| author2 |
Fontecha-Barriuso, Miguel Martin-Sanchez, Diego Guerrero-Mauvecin, Juan Goma-Garces, Elena Fernández Fernández, Beatriz Carriazo, Sol Sánchez Niño, María Dolores Ramos, Adrian M. Ruiz Ortega, Marta Ortiz Arduán, Alberto Sanz, Ana Belén |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Farmacología Departamento de Medicina Facultad de Medicina Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) |
| dc.subject.none.fl_str_mv |
Apabetalone BET Chronic kidney disease Crotonylation Diabetes Diabetic kidney disease DNA methylation Epigenetic Farmacia Medicina |
| topic |
Apabetalone BET Chronic kidney disease Crotonylation Diabetes Diabetic kidney disease DNA methylation Epigenetic Farmacia Medicina |
| 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. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-06-09 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/694819 https://dx.doi.org/10.3390/ijms21114113 |
| url |
http://hdl.handle.net/10486/694819 https://dx.doi.org/10.3390/ijms21114113 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI, Basel, SMwitzerland |
| publisher.none.fl_str_mv |
MDPI, Basel, SMwitzerland |
| dc.source.none.fl_str_mv |
reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
| instname_str |
Universidad Autónoma de Madrid |
| reponame_str |
Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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1869422990372896768 |
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15,301603 |