{rfName}

Indexed in

License and use

Citations

2

Altmetrics

Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Gratacós-Ginès JAuthorPose EAuthorBataller RAuthor
Share
Publications
>
Article

Modulatory effects of CNNM4 on Protein-L-Isoaspartyl-O-Methyltransferase repair function during Alcohol-Induced hepatic damage.

Publicated to:Hepatology. - 2024-12-06 (), DOI: 10.1097/HEP.0000000000001156

Authors: Irene González‐Recio; Naroa Goikoetxea‐Usandizaga; Claudia M. Rejano-Gordillo; Carolina Conter; Rubén Rodríguez Agudo; Marina Serrano‐Maciá; Leidy Estefanía Zapata-Pavas; Patricia Peña-Sanfélix; Mikel Azkargorta; Félix Elortza; José M. Herranz; Álex Guillamon Thiery; Armando Ruiz; Ramiro Jover; Unai Galicia García; César Martı́n; Ute Schaeper; Teresa C. Delgado; Irene Díaz‐Moreno; Antonio Díaz‐Quintana; D. Buccella; Rubén Nogueiras; Josepmaría Argemí; Matías A. Ávila; Jordi Gratacós‐Ginès; Paula Iruzubieta; Elisa Pose; Ramón Bataller; Javier Crespo; Luis Alfonso Martínez‐Cruz; María Luz Martínez‐Chantar

Affiliations

Biofisika Institute, Consejo Superior de Investigaciones Científicas (CSIC), Departamento Bioquímica y Biología Molecular, Facultad de Ciencia y Tecnología, Universidad del País Vasco (UPV/EHU), Leioa, Spain. - Author
Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA. - Author
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain. - Author
Clinical Biochemistry Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain. - Author
Departamento de Bioquímica Vegetal y Biologia Molecular, Facultad de Biología, Universidad de Sevilla, C. San Fernando 4, 41004 Sevilla (Spain). - Author
Department of Chemistry, New York University, New York, New York 10003, United States. - Author
Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, Santander, Spain. - Author
Hepatology Program, Centro de Investigacion Medica Aplicada (CIMA), Liver Unit, Clinica Universidad de Navarra (CUN), Instituto de Investigacion de Navarra (IdisNA), University of Navarra, Pamplona, Spain. - Author
Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain. - Author
Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, Barcelona, Catalonia, Spain. - Author
Institute for Chemical Research (IIQ), Scientific Research Centre "Isla de la Cartuja" (cicCartuja), University of Seville - CSIC, Avda. Américo Vespucio 49, 41092 Seville, Spain. - Author
Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain. - Author
Molecular Metabolism Lab, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Av. Barcelona, Campus Vida, Santiago de Compostela University, 15782 Santiago de Compostela, Spain. - Author
Proteomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain. - Author
Silence Therapeutics GmbH, Berlin, Robert Rössle Strasse 10, 13125, Berlin, Germany. - Author
See more

Abstract

Alcohol-related liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg2+) deficiency, which can influence the liver disease progression. The mechanisms underlying Mg2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in ALD patients and preclinical animal models. In this study, CNNM4 is upregulated in the liver of both ALD patients and animal models. CNNM4 overexpression triggers Mg²⁺ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N-acetylgalactosamine (GalNAc) silencing RNA (siRNA) technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating ER stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases SAMe levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment. These findings shed light on the dysregulation of Mg2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. GalNAc siCnnm4 therapy boost the repair processes of ethanol damaged proteins through the upregulation of PCMT1 activity.

Keywords
Good health and well-being

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Hepatology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 7/143, thus managing to position itself as a Q1 (Primer Cuartil), in the category Gastroenterology & Hepatology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-04-26:

  • Scopus: 2
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-04-26:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 5.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 5 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.25.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Good Health And Well-being, with a probability of 89% according to the mBERT algorithm developed by Aurora University.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany.