Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis

Nat Metab. 2020 Jun;2(6):514-531. doi: 10.1038/s42255-020-0214-9. Epub 2020 Jun 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Carbon Tetrachloride Poisoning / metabolism
  • Diet, High-Fat
  • Diet, Western
  • Hepatic Stellate Cells / metabolism
  • Humans
  • Inflammation / genetics
  • Liver Regeneration / drug effects
  • Liver Regeneration / genetics
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Recombinant Proteins / pharmacology
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism
  • Wound Healing / genetics


  • BMP8B protein, human
  • Bmp8b protein, mouse
  • Bone Morphogenetic Proteins
  • Recombinant Proteins
  • Smad Proteins
  • Transforming Growth Factor beta