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

Nature Metabolism
Michele VaccaAntonio Vidal-Puig

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.

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Citations

Jun 25, 2020·Nature Reviews. Endocrinology·Alan Morris
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Jul 7, 2021·Alternatives to Laboratory Animals : ATLA·Bhumika SinghJohn Malcolm Wilkinson

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Methods Mentioned

BETA
biopsies
immuno-profiling
nuclear magnetic resonance
Assay
enzyme-linked immunosorbent assays
ELISA
PCR
RNA-Seq

Software Mentioned

BestKeeper
EdgeR
XCMS
Indica Lab HALO
ImmGem
ImageJ
MSConvert
R
ImmQuant
Bioconductor

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