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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-08

AUTHORS

Michele Vacca, Jack Leslie, Samuel Virtue, Brian Y. H. Lam, Olivier Govaere, Dina Tiniakos, Sophie Snow, Susan Davies, Kasparas Petkevicius, Zhen Tong, Vivian Peirce, Mette Juul Nielsen, Zsuzsanna Ament, Wei Li, Tomasz Kostrzewski, Diana Julie Leeming, Vlad Ratziu, Michael E. D. Allison, Quentin M. Anstee, Julian L. Griffin, Fiona Oakley, Antonio 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. More... »

PAGES

514-531

References to SciGraph publications

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  • Journal

    TITLE

    Nature Metabolism

    ISSUE

    6

    VOLUME

    2

    Author Affiliations

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s42255-020-0214-9

    DOI

    http://dx.doi.org/10.1038/s42255-020-0214-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1128293944

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32694734


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