TY - JOUR
TI - Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis
AU - Vacca, M.
AU - Leslie, J.
AU - Virtue, S.
AU - Lam, B.Y.H.
AU - Govaere, O.
AU - Tiniakos, D.
AU - Snow, S.
AU - Davies, S.
AU - Petkevicius, K.
AU - Tong, Z.
AU - Peirce, V.
AU - Nielsen, M.J.
AU - Ament, Z.
AU - Li, W.
AU - Kostrzewski, T.
AU - Leeming, D.J.
AU - Ratziu, V.
AU - Allison, M.E.D.
AU - Anstee, Q.M.
AU - Griffin, J.L.
AU - Oakley, F.
AU - Vidal-Puig, A.
JO - Nature Metabolism
PY - 2020
VL - 2
TODO - 6
SP - 514-531
PB - Lithuanian Nature Research Centre
SN - null
TODO - 10.1038/s42255-020-0214-9
TODO - 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
TODO - 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.
ER -