Epigenetic regulation of inflammatory processes associated with chronic kidney damage. Identification of new therapeutic targets. (Q3137941): Difference between revisions
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(Created claim: summary (P836): Chronic kidney disease (CKD) is a major international public health problem with a high incidence in our society. In Spain, around 4 million people suffer from CRD and every year 6,000 patients progress to dialysis or renal transplantation. The etiology of CKD is very different, but in all cases it has associated a high inflammatory and pro-fibrotic component. The current treatments are not able to prevent the progression of the disease, it is n...) |
(Changed label, description and/or aliases in en: translated_label) |
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Epigenetic regulation of inflammatory processes associated with chronic kidney damage. Identification of new therapeutic targets. | |||
Revision as of 12:32, 12 October 2021
Project Q3137941 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Epigenetic regulation of inflammatory processes associated with chronic kidney damage. Identification of new therapeutic targets. |
Project Q3137941 in Spain |
Statements
41,600.0 Euro
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52,000.0 Euro
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80.0 percent
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1 January 2018
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31 March 2021
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FUNDACION PARA LA INVESTIGACION E INNOVACION BIOSANITARIA EN EL PRINCIPADO DE ASTURIAS
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43°21'38.16"N, 5°50'41.64"W
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33044
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La enfermedad renal crónica (ERC) es un importante problema de salud pública internacional con una alta incidencia en nuestra sociedad. En España, alrededor de 4 millones de personas padecen de ERC y cada año 6000 pacientes progresan hasta necesitar diálisis o un trasplante renal. La etiología de la ERC es muy diferente, pero en todos los casos lleva asociada un alto componente inflamatorio y pro-fibrótico. Los tratamientos actuales no son capaces de evitar la progresión de la enfermedad, siendo necesaria la búsqueda de nuevas dianas terapéuticas desde estrategias diferentes y que puedan ser fácilmente trasladadas al paciente. Nuestra propuesta es que los mecanismos epigenéticos relacionados con las dinámicas de acetilación en histonas y factores de transcripción son esenciales en desencadenar la inflamación que conduce al daño renal. Se proponen dos abordajes; la modulación farmacológica de P300/CBP y la regulación a través de los ácidos grasos de cadena corta (AGCC) derivados de la microbiota intestinal. En concreto estudiaremos i) el efecto in vivo e in vitro de los inhibidores de P300/CBP en los procesos inflamatorios, ii) las dinámicas de acetilación inducidas por P300/CBP en combinación con las proteínas BET y complejos remodeladores de la cromatina, iii) la regulación del inflamasoma mediada por P300/CBP en macrógafos y su papel en la polarización M1/M2, y iv) el papel de los AGCC como inhibidores de las histonas deacetilasas en las diversas rutas de inflamación (NF-kB e inflamasoma) . La Epigenética es un campo emergente en la ERC y la modulación de sus mecanismos por fármacos (CBP30/JQ1) o cambios en la dieta (prebióticos/fibras) supondrá un nuevo abordaje para el tratamiento de la ERC. Este proyecto forma parte de la REDINREN 3.0 (ISCIII). (Spanish)
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Chronic kidney disease (CKD) is a major international public health problem with a high incidence in our society. In Spain, around 4 million people suffer from CRD and every year 6,000 patients progress to dialysis or renal transplantation. The etiology of CKD is very different, but in all cases it has associated a high inflammatory and pro-fibrotic component. The current treatments are not able to prevent the progression of the disease, it is necessary to search for new therapeutic targets from different strategies and that can be easily transferred to the patient. Our proposal is that epigenetic mechanisms related to acetylation dynamics in histones and transcription factors are essential in triggering inflammation leading to kidney damage. Two approaches are proposed; pharmacological modulation of P300/CBP and regulation through short chain fatty acids (CCFAs) derived from the intestinal microbiota. In particular, we will study i) the in vivo and in vitro effect of P300/CBP inhibitors on inflammatory processes, ii) P300/CBP induced acetylation dynamics in combination with BET proteins and chromatin remodeling complexes, iii) P300/CBP-mediated inflammatory regulation in macrogaphs and their role in M1/M2 polarisation, and iv) the role of AGCC as inhibitors of histone deacetylase in the various inflammation pathways (NF-kB and inflammatory). Epigenetics is an emerging field in CRD and modulation of its mechanisms by drugs (CBP30/JQ1) or dietary changes (prebiotics/fibers) will be a new approach to the treatment of CRD. This project is part of REDINREN 3.0 (ISCIII). (English)
12 October 2021
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Oviedo
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Identifiers
PI17_01244
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