Person: Regueiro González-Barros, José Ramón
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First Name
José Ramón
Last Name
Regueiro González-Barros
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Inmunología
Identifiers
3 results
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Item Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis(Cell death diseases, 2023) Kang, Zheng; Fengjie, Hao; Medrano García, Sandra; Chaobo, Chen; Morán Blanco, Laura; Peligros Gómez, María Isabel; Vaquero Martín, Francisco Javier; Bañares Cañizares, Rafael; Gómez Del Moral Martín-Consuegra, Manuel María; Regueiro González-Barros, José Ramón; Martínez Naves, Eduardo; Nevzorova, Yulia; Fernández Malavé, Edgar Gonzalo; Cubero Palero, Francisco JavierProgressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.Item Fat: quality or quantity? What matters most for the progression of Metabolic Associated Fatty Liver Disease (MAFLD).(Biomedicines, 2021) Estévez Vázquez, Olga; Benede Ubieto, Raquel; Sanz García, Carlos; Maranillo Alcaide, Eva; Sañudo Tejero, José Ramón; Vázquez Osorio, María Teresa; Lamas Paz, Arantza; Peligros Gómez, María Isabel; Vaquero, Javier; Martínez Naves, Eduardo; Regueiro González-Barros, José Ramónfirst_pagesettingsOrder Article Reprints Open AccessArticle Fat: Quality, or Quantity? What Matters Most for the Progression of Metabolic Associated Fatty Liver Disease (MAFLD) by Olga Estévez-Vázquez 1,2ORCID,Raquel Benedé-Ubieto 1,2,Feifei Guo 2,Beatriz Gómez-Santos 3ORCID,Patricia Aspichueta 3,4,5ORCID,Johanna Reissing 6,Tony Bruns 6ORCID,Carlos Sanz-García 2ORCID,Svenja Sydor 7ORCID,Lars P. Bechmann 7,Eva Maranillo 8,José Ramón Sañudo 8,María Teresa Vázquez 8,Arantza Lamas-Paz 2ORCID,Laura Morán 2,9,Marina S. Mazariegos 2,Andreea Ciudin 10ORCID,Juan M. Pericàs 5,11,María Isabel Peligros 12,Javier Vaquero 5,9,13ORCID,add Show full author list 1 Department of Physiology, Genetics and Microbiology, Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain 2 Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain 3 Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, 48940 Leioa, Spain 4 Biocruces Health Research Institute, 48903 Barakaldo, Spain 5 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, 28220 Madrid, Spain 6 Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany 7 Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, 44801 Bochum, Germany 8 Department of Human Anatomy and Embryology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain 9 Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain 10 Endocrinology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute for Research (VHIR), 08035 Barcelona, Spain add Show full affiliation list * Author to whom correspondence should be addressed. † These authors contributed equally to this work. Biomedicines 2021, 9(10), 1289; https://doi.org/10.3390/biomedicines9101289 Submission received: 12 August 2021 / Revised: 13 September 2021 / Accepted: 19 September 2021 / Published: 22 September 2021 (This article belongs to the Special Issue Metabolic Syndrome and NASH: From Molecular Basis to Therapy) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Objectives: Lately, many countries have restricted or even banned transfat, and palm oil has become a preferred replacement for food manufacturers. Whether palm oil is potentially an unhealthy food mainly due to its high content of saturated Palmitic Acid (PA) is a matter of debate. The aim of this study was to test whether qualitative aspects of diet such as levels of PA and the fat source are risk factors for Metabolic Syndrome (MS) and Metabolic Associated Fatty Liver Disease (MAFLD). Methods: C57BL/6 male mice were fed for 14 weeks with three types of Western diet (WD): 1. LP-WD—low concentration of PA (main fat source—corn and soybean oils); 2. HP-WD—high concentration of PA (main fat source—palm oil); 3. HP-Trans-WD—high concentration of PA (mainly transfat). Results: All types of WD caused weight gain, adipocyte enlargement, hepatomegaly, lipid metabolism alterations, and steatohepatitis. Feeding with HP diets led to more prominent obesity, hypercholesterolemia, stronger hepatic injury, and fibrosis. Only the feeding with HP-Trans-WD resulted in glucose intolerance and elevation of serum transaminases. Brief withdrawal of WDs reversed MS and signs of MAFLD. However, mild hepatic inflammation was still detectable in HP groups. Conclusions: HP and HP-Trans-WD play a crucial role in the genesis of MS and MAFLD.Item Abnormal Liver Function Test in Patients Infected with Coronavirus (SARS-CoV-2): A Retrospective Single-Center Study from Spain(Journal of Clinical Medicine, 2021) Benede Ubieto, Raquel; Estévez Vázquez, Olga; Martínez Naves, Eduardo; Regueiro González-Barros, José Ramón; Cubero Palero, Francisco Javier; Nevzorova, YuliaThe outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.