@article{3077817,
    title = "Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis",
    author = "Vacca, M. and Leslie, J. and Virtue, S. and Lam, B.Y.H. and Govaere, O. and Tiniakos, D. and Snow, S. and Davies, S. and Petkevicius, K. and Tong, Z. and Peirce, V. and Nielsen, M.J. and Ament, Z. and Li, W. and Kostrzewski, T. and Leeming, D.J. and Ratziu, V. and Allison, M.E.D. and Anstee, Q.M. and Griffin, J.L. and Oakley, F. and Vidal-Puig, A.",
    journal = "Nature Metabolism",
    year = "2020",
    volume = "2",
    number = "6",
    pages = "514-531",
    publisher = "Lithuanian Nature Research Centre",
    doi = "10.1038/s42255-020-0214-9",
    keywords = "bone morphogenetic protein;  bone morphogenetic protein 8B;  gelatinase B;  inflammasome;  Smad1 protein;  Smad2 protein;  Smad3 protein;  Smad5 protein;  transforming growth factor beta;  unclassified drug;  vasculotropin;  BMP8B protein, human;  Bmp8b protein, mouse;  bone morphogenetic protein;  recombinant protein;  Smad protein;  transforming growth factor beta, AML12 cell line;  animal experiment;  animal model;  animal tissue;  Article;  bioinformatics;  calorimetry;  carbon tetrachloride-induced liver injury;  cell activation;  cell differentiation;  cell isolation;  cell proliferation;  controlled study;  energy expenditure;  gene expression;  glucose metabolism;  hepatic stellate cell;  histopathology;  human;  human cell;  immunofluorescence;  immunohistochemistry;  in situ hybridization;  lipid metabolism;  mouse;  nonalcoholic fatty liver;  nonhuman;  partial hepatectomy;  phenotype;  phosphoproteomics;  prevalence;  priority journal;  protein expression;  proteomics;  reverse transcription polymerase chain reaction;  risk factor;  RNA extraction;  RNA sequence;  RNA sequencing;  signal transduction;  transcriptomics;  upregulation;  animal;  C57BL mouse;  drug effect;  genetics;  inflammation;  intoxication;  lipid diet;  liver regeneration;  metabolism;  nonalcoholic fatty liver;  Western diet;  wound healing, Animals;  Bone Morphogenetic Proteins;  Carbon Tetrachloride Poisoning;  Diet, High-Fat;  Diet, Western;  Hepatic Stellate Cells;  Humans;  Inflammation;  Liver Regeneration;  Mice;  Mice, Inbred C57BL;  Non-alcoholic Fatty Liver Disease;  Recombinant Proteins;  Smad Proteins;  Transforming Growth Factor beta;  Wound Healing",
    abstract = "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 (TGFβ)–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 TGFβ–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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited."
}