Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis
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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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BMP8B is upregulated in MASH and signals through SMADs to drive HSC activation in animal models.
“Another ligand of the TGFβ-bone morphogenetic protein (BMP) superfamily, bone morphogenetic protein 8B (BMP8B), is upregulated in MASH and signals through mothers against decapentaplegic (SMADs) to drive HSC activation in animal models, reinforcing TGFβ's vital role as a fibrogenic stimulus (150).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [150]
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- Authors
- Vacca, M., Leslie, J., Virtue, S., Lam, B. Y. H., Govaere, O., Tiniakos, D., Snow, S., Davies, S., Petkevicius, K., Tong, Z., Peirce, V., Nielsen, M. J., Ament, Z., Li, W., Kostrzewski, T., Leeming, D. J., Ratziu, V., Allison, M. E. D., Anstee, Q. M., Griffin, J. L., Oakley, F., & Vidal-Puig, A.
- Affiliations
- Newcastle University (GB)
- University of Cambridge (GB)
- National and Kapodistrian University of Athens (GR)
- CN Bio Innovations (United Kingdom) (GB)
- Nordic Bioscience (Denmark) (DK)
- Sorbonne Université (FR)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- ORCID
- Venue
- Nature Metabolism
- Published
- 2020-06-08
- Volume
- 2
- Issue
- 6
- Pages
- 514-531
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC7617436
- OpenAlex
- W3027189358
- Cited by
- 60
- References
- 64
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 5
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lirias (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Fondazione Umberto Veronesi (Post-Doctoral Fellowship)
- DH | National Institute for Health Research (Pump-Priming Grant NIHR-BRC Cambridge Gastro, NIHR Cambridge Biomedical Research Centre)
- EC | Horizon 2020 Framework Programme (GA 634413)
- RCUK | Medical Research Council (MC_PC_13030, PO 4050281695, MC UP A90 1006, MR/K0019494/1 & MR/R023026/1, MRC DMC MC UU 12012/2)
- Cancer Research UK (C18342/A23390)
- Evelyn Trust
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- nonalcoholic steatohepatitis, BMP8B, TGF-β/BMP signaling, hepatic stellate cells, liver fibrosis, liver inflammation, wound healing, Smad2/3 signaling, Smad1/5/9 signaling, NASH progression, therapeutic target
- MeSH terms
- Animals, Carbon Tetrachloride Poisoning, Humans, Inflammation, Liver Regeneration, Mice, Inbred C57BL, Recombinant Proteins, Wound Healing, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Mice, Smad Proteins, Hepatic Stellate Cells, Diet, High-Fat, Non-alcoholic Fatty Liver Disease, Diet, Western
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