Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1
Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of alcohol metabolism given excessive...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923002495 |
| _version_ | 1827378172933439488 |
|---|---|
| author | Rubén Rodríguez-Agudo Irene González-Recio Marina Serrano-Maciá Miren Bravo Petar Petrov Delia Blaya Jose María Herranz María Mercado-Gómez Claudia María Rejano-Gordillo Sofía Lachiondo-Ortega Clàudia Gil-Pitarch Mikel Azkargorta Sebastiaan Martijn Van Liempd Luis Alfonso Martinez-Cruz A.L. Simão Félix Elortza César Martín Yulia A. Nevzorova Francisco Javier Cubero Teresa C. Delgado Josepmaria Argemi Ramón Bataller Kristina Schoonjans Jesús M. Banales Rui E. Castro Pau Sancho-Bru Matías A. Avila Josep Julve Ramiro Jover Jon Mabe Jorge Simon Naroa Goikoetxea-Usandizaga María L. Martínez-Chantar |
| author_facet | Rubén Rodríguez-Agudo Irene González-Recio Marina Serrano-Maciá Miren Bravo Petar Petrov Delia Blaya Jose María Herranz María Mercado-Gómez Claudia María Rejano-Gordillo Sofía Lachiondo-Ortega Clàudia Gil-Pitarch Mikel Azkargorta Sebastiaan Martijn Van Liempd Luis Alfonso Martinez-Cruz A.L. Simão Félix Elortza César Martín Yulia A. Nevzorova Francisco Javier Cubero Teresa C. Delgado Josepmaria Argemi Ramón Bataller Kristina Schoonjans Jesús M. Banales Rui E. Castro Pau Sancho-Bru Matías A. Avila Josep Julve Ramiro Jover Jon Mabe Jorge Simon Naroa Goikoetxea-Usandizaga María L. Martínez-Chantar |
| author_sort | Rubén Rodríguez-Agudo |
| collection | DOAJ |
| description | Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of alcohol metabolism given excessive acetate and NAD depletion and play an important role in liver injury. In this regard, novel therapeutic approaches based on epigenetic modulators are increasingly proposed. MicroRNAs, epigenetic modulators acting at the post-transcriptional level, appear to be promising new targets for the treatment of ALD. Methods: MiR-873-5p levels were measured in 23 liver tissue from Patients with ALD, and GNMT levels during ALD were confirmed using expression databases (transcriptome n = 62, proteome n = 68). High-resolution proteomics and metabolomics in mice following the Gao-binge model were used to investigate miR-873-5p expression in ALD. Hepatocytes exposed to 50 mM alcohol for 12 h were used to study toxicity. The effect of anti-miR-873-5p in the treatment outcomes of ALD was investigated. Results: The analysis of human and preclinical ALD samples revealed increased expression of miR-873-5p in the liver. Interestingly, there was an inverse correlation with NNMT, suggesting a novel mechanism for NAD depletion and aberrant acetylation during ALD progression. High-resolution proteomics and metabolomics identified miR-873-5p as a key regulator of NAD metabolism and SIRT1 deacetylase activity. Anti-miR-873-5p reduced NNMT activity, fuelled the NAD salvage pathway, restored the acetylome, and modulated the levels of NF-κB and FXR, two known SIRT1 substrates, thereby protecting the liver from apoptotic and inflammatory processes, and improving bile acid homeostasis. Conclusions: These data indicate that targeting miR-873-5p, a repressor of GNMT previously associated with NAFLD and acetaminophen-induced liver failure. is a novel and attractive approach to treating alcohol-induced hepatoxicity. Impact and implications: The role of miR-873-5p has not been explicitly examined in the progression of ALD, a pathology with no therapeutic options. In this study, inhibiting miR-873-5p exerted hepatoprotective effects against ALD through rescued SIRT1 activity and consequently restored bile acid homeostasis and attenuated the inflammatory response. Targeting hepatic miR-873-5p may represent a novel therapeutic approach for the treatment of ALD. |
| first_indexed | 2024-03-08T12:52:06Z |
| format | Article |
| id | doaj.art-2c731ca37cd542a581f44cda78d386a6 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-08T12:52:06Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-2c731ca37cd542a581f44cda78d386a62024-01-20T04:46:13ZengElsevierJHEP Reports2589-55592024-01-0161100918Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1Rubén Rodríguez-Agudo0Irene González-Recio1Marina Serrano-Maciá2Miren Bravo3Petar Petrov4Delia Blaya5Jose María Herranz6María Mercado-Gómez7Claudia María Rejano-Gordillo8Sofía Lachiondo-Ortega9Clàudia Gil-Pitarch10Mikel Azkargorta11Sebastiaan Martijn Van Liempd12Luis Alfonso Martinez-Cruz13A.L. Simão14Félix Elortza15César Martín16Yulia A. Nevzorova17Francisco Javier Cubero18Teresa C. Delgado19Josepmaria Argemi20Ramón Bataller21Kristina Schoonjans22Jesús M. Banales23Rui E. Castro24Pau Sancho-Bru25Matías A. Avila26Josep Julve27Ramiro Jover28Jon Mabe29Jorge Simon30Naroa Goikoetxea-Usandizaga31María L. Martínez-Chantar32Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Experimental Hepatology Joint Research Unit, IIS Hospital La Fe and Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Liver Cell Plasticity and Tissue Repair Lab, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Proteomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, SpainMetabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, PortugalCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Proteomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, SpainBiofisika Institute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Leioa, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Department of Immunology, Ophthalmology and ENT Complutense University School of Medicine Madrid Spain, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Department of Internal Medicine III, University Hospital RWTH Aachen, GermanyCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Department of Immunology, Ophthalmology and ENT Complutense University School of Medicine Madrid Spain, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra-IdiSNA, Pamplona, SpainDivision of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Liver Research Center, Pittsburgh, Pennsylvania, USAInstitute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, San Sebastian, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, SpainResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, PortugalCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Liver Cell Plasticity and Tissue Repair Lab, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain; Hepatology Program, Cima-University of Navarra, Pamplona, SpainInstitut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Experimental Hepatology Joint Research Unit, IIS Hospital La Fe and Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, SpainBusiness Department, IK4-Tekniker, Eibar, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Corresponding authors. Addresses: CIC bioGUNE, Ed. 801A Parque Tecnológico de Bizkaia, Derio, Bizkaia, Spain. Tel.: +944 061 318 (M.L. Martínez-Chantar); CIC bioGUNE, Ed. 801A Parque Tecnológico de Bizkaia, 48160 Derio, Bizkaia, Spain. Tel.: +944 061 318 (N. Goikoetxea-Usandizaga).Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain; Corresponding authors. Addresses: CIC bioGUNE, Ed. 801A Parque Tecnológico de Bizkaia, Derio, Bizkaia, Spain. Tel.: +944 061 318 (M.L. Martínez-Chantar); CIC bioGUNE, Ed. 801A Parque Tecnológico de Bizkaia, 48160 Derio, Bizkaia, Spain. Tel.: +944 061 318 (N. Goikoetxea-Usandizaga).Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of alcohol metabolism given excessive acetate and NAD depletion and play an important role in liver injury. In this regard, novel therapeutic approaches based on epigenetic modulators are increasingly proposed. MicroRNAs, epigenetic modulators acting at the post-transcriptional level, appear to be promising new targets for the treatment of ALD. Methods: MiR-873-5p levels were measured in 23 liver tissue from Patients with ALD, and GNMT levels during ALD were confirmed using expression databases (transcriptome n = 62, proteome n = 68). High-resolution proteomics and metabolomics in mice following the Gao-binge model were used to investigate miR-873-5p expression in ALD. Hepatocytes exposed to 50 mM alcohol for 12 h were used to study toxicity. The effect of anti-miR-873-5p in the treatment outcomes of ALD was investigated. Results: The analysis of human and preclinical ALD samples revealed increased expression of miR-873-5p in the liver. Interestingly, there was an inverse correlation with NNMT, suggesting a novel mechanism for NAD depletion and aberrant acetylation during ALD progression. High-resolution proteomics and metabolomics identified miR-873-5p as a key regulator of NAD metabolism and SIRT1 deacetylase activity. Anti-miR-873-5p reduced NNMT activity, fuelled the NAD salvage pathway, restored the acetylome, and modulated the levels of NF-κB and FXR, two known SIRT1 substrates, thereby protecting the liver from apoptotic and inflammatory processes, and improving bile acid homeostasis. Conclusions: These data indicate that targeting miR-873-5p, a repressor of GNMT previously associated with NAFLD and acetaminophen-induced liver failure. is a novel and attractive approach to treating alcohol-induced hepatoxicity. Impact and implications: The role of miR-873-5p has not been explicitly examined in the progression of ALD, a pathology with no therapeutic options. In this study, inhibiting miR-873-5p exerted hepatoprotective effects against ALD through rescued SIRT1 activity and consequently restored bile acid homeostasis and attenuated the inflammatory response. Targeting hepatic miR-873-5p may represent a novel therapeutic approach for the treatment of ALD.http://www.sciencedirect.com/science/article/pii/S2589555923002495Alcohol-related liver diseaseNIAAA modelmicroRNASIRT1Nicotinamide adenine dinucleotide salvage pathway |
| spellingShingle | Rubén Rodríguez-Agudo Irene González-Recio Marina Serrano-Maciá Miren Bravo Petar Petrov Delia Blaya Jose María Herranz María Mercado-Gómez Claudia María Rejano-Gordillo Sofía Lachiondo-Ortega Clàudia Gil-Pitarch Mikel Azkargorta Sebastiaan Martijn Van Liempd Luis Alfonso Martinez-Cruz A.L. Simão Félix Elortza César Martín Yulia A. Nevzorova Francisco Javier Cubero Teresa C. Delgado Josepmaria Argemi Ramón Bataller Kristina Schoonjans Jesús M. Banales Rui E. Castro Pau Sancho-Bru Matías A. Avila Josep Julve Ramiro Jover Jon Mabe Jorge Simon Naroa Goikoetxea-Usandizaga María L. Martínez-Chantar Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1 JHEP Reports Alcohol-related liver disease NIAAA model microRNA SIRT1 Nicotinamide adenine dinucleotide salvage pathway |
| title | Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1 |
| title_full | Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1 |
| title_fullStr | Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1 |
| title_full_unstemmed | Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1 |
| title_short | Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1 |
| title_sort | anti mir 873 5p improves alcohol related liver disease by enhancing hepatic deacetylation via sirt1 |
| topic | Alcohol-related liver disease NIAAA model microRNA SIRT1 Nicotinamide adenine dinucleotide salvage pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923002495 |
| work_keys_str_mv | AT rubenrodriguezagudo antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT irenegonzalezrecio antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT marinaserranomacia antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT mirenbravo antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT petarpetrov antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT deliablaya antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT josemariaherranz antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT mariamercadogomez antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT claudiamariarejanogordillo antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT sofialachiondoortega antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT claudiagilpitarch antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT mikelazkargorta antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT sebastiaanmartijnvanliempd antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT luisalfonsomartinezcruz antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT alsimao antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT felixelortza antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT cesarmartin antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT yuliaanevzorova antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT franciscojaviercubero antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT teresacdelgado antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT josepmariaargemi antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT ramonbataller antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT kristinaschoonjans antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT jesusmbanales antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT ruiecastro antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT pausanchobru antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT matiasaavila antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT josepjulve antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT ramirojover antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT jonmabe antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT jorgesimon antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT naroagoikoetxeausandizaga antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 AT marialmartinezchantar antimir8735pimprovesalcoholrelatedliverdiseasebyenhancinghepaticdeacetylationviasirt1 |