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Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis.
Vacca, Michele; Leslie, Jack; Virtue, Samuel; Lam, Brian Y H; Govaere, Olivier; Tiniakos, Dina; Snow, Sophie; Davies, Susan; Petkevicius, Kasparas; Tong, Zhen; Peirce, Vivian; Nielsen, Mette Juul; Ament, Zsuzsanna; Li, Wei; Kostrzewski, Tomasz; Leeming, Diana Julie; Ratziu, Vlad; Allison, Michael E D; Anstee, Quentin M; Griffin, Julian L; Oakley, Fiona; Vidal-Puig, Antonio.
Afiliación
  • Vacca M; TVP Lab, WT/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK. mv400@medschl.cam.ac.uk.
  • Leslie J; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK. mv400@medschl.cam.ac.uk.
  • Virtue S; Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Lam BYH; TVP Lab, WT/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
  • Govaere O; Yeo Group and Genomics and Transcriptomics Core, WT/MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Tiniakos D; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Snow S; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Davies S; Department of Pathology, Aretaieion Hospital, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
  • Petkevicius K; CN Bio Innovations Limited, Cambridge, UK.
  • Tong Z; Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, UK.
  • Peirce V; TVP Lab, WT/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
  • Nielsen MJ; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Ament Z; TVP Lab, WT/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit - Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
  • Li W; Nordic Bioscience A/S, Herlev, Denmark.
  • Kostrzewski T; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.
  • Leeming DJ; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Ratziu V; CN Bio Innovations Limited, Cambridge, UK.
  • Allison MED; Nordic Bioscience A/S, Herlev, Denmark.
  • Anstee QM; Sorbonne Université, Institute for Cardiometabolism and Nutrition (ICAN), Hôpital Pitié-Salpêtrière, Paris, France.
  • Griffin JL; Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University Hospitals, Cambridge, UK.
  • Oakley F; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Vidal-Puig A; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Nat Metab ; 2(6): 514-531, 2020 06.
Article en En | MEDLINE | ID: mdl-32694734
Non-alcoholic steatohepatitis (NASH) is characterized by lipotoxicity, inflammation and fibrosis, ultimately leading to end-stage liver disease. The molecular mechanisms promoting NASH are poorly understood, and treatment options are limited. Here, we demonstrate that hepatic expression of bone morphogenetic protein 8B (BMP8B), a member of the transforming growth factor beta (TGFß)-BMP superfamily, increases proportionally to disease stage in people and animal models with NASH. BMP8B signals via both SMAD2/3 and SMAD1/5/9 branches of the TGFß-BMP pathway in hepatic stellate cells (HSCs), promoting their proinflammatory phenotype. In vivo, the absence of BMP8B prevents HSC activation, reduces inflammation and affects the wound-healing responses, thereby limiting NASH progression. Evidence is featured in primary human 3D microtissues modelling NASH, when challenged with recombinant BMP8. Our data show that BMP8B is a major contributor to NASH progression. Owing to the near absence of BMP8B in healthy livers, inhibition of BMP8B may represent a promising new therapeutic avenue for NASH treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Morfogenéticas Óseas / Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Metab Año: 2020 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Morfogenéticas Óseas / Enfermedad del Hígado Graso no Alcohólico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Metab Año: 2020 Tipo del documento: Article Pais de publicación: Alemania