ArticleLiver international : official journal of the International Association for the Study of the Liver2018
Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Systematic review of the mechanism and assessment of liver fibrosis in biliary atresia.Pediatric surgery international · 2024Pooled it
- Moderate increase of MET in hepatocytes protects against cholestatic liver injury by promoting an effective antioxidant response.The FEBS journal · 2026Article
- Bone morphogenetic protein (BMP)-9, a systemic homeostasis factor with diverse functions in the liver and beyond.Bioscience reports · 2025Review
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Unveiling the Impact of BMP9 in Liver Diseases: Insights into Pathogenesis and Therapeutic Potential.Biomolecules · 2024Review
- Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury.International journal of biological sciences · 2024Article
- Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.Cell insight · 2023Review
- Circulating bone morphogenetic protein 8A is a novel biomarker to predict advanced liver fibrosis.Biomarker research · 2023Article
- Unveiling the power of microenvironment in liver regeneration: an in-depth overview.Frontiers in genetics · 2023Review
- The potential regulatory role of BMP9 in inflammatory responses.Genes & diseases · 2022Review
- Article
- New insights into BMP9 signaling in liver diseases.Molecular and cellular biochemistry · 2021Review
- BMP9-ID1 signaling promotes EpCAM-positive cancer stem cell properties in hepatocellular carcinoma.Molecular oncology · 2021Article
- Exogenous BMP9 promotes lung fibroblast HFL-1 cell activation via ALK1/Smad1/5 signalingExperimental and therapeutic medicine · 2021Article
- Molecular pathways of liver regeneration: A comprehensive review.World journal of hepatology · 2021Review
- Current and Emerging Approaches for Hepatic Fibrosis Treatment.Gastroenterology research and practice · 2021Review
- Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe?GeroScience · 2020Review
- Article
- Reduced circulating BMP10 and BMP9 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis.EBioMedicine · 2020Article
- A Signaling Crosstalk between BMP9 and HGF/c-Met Regulates Mouse Adult Liver Progenitor Cell Survival.Cells · 2020Article
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsBone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion.
methodsWT and BMP9KO mice were submitted to DDC diet. Livers were examined for liver injury, fibrosis, inflammation and oval cell expansion by serum biochemistry, histology, RT-qPCR and western blot. BMP9 signalling and effects in oval cells were studied in vitro using western blot and transcriptional assays, plus functional assays of DNA synthesis, cell viability and apoptosis. Crosslinking assays and short hairpin RNA approaches were used to identify the receptors mediating BMP9 effects.
resultsDeletion of BMP9 reduces liver damage and fibrosis, but enhances inflammation upon DDC feeding. Molecularly, absence of BMP9 results in overactivation of PI3K/AKT, ERK-MAPKs and c-Met signalling pathways, which together with an enhanced ductular reaction and oval cell expansion evidence an improved regenerative response and decreased damage in response to DDC feeding. Importantly, BMP9 directly targets oval cells, it activates SMAD1,5,8, decreases cell growth and promotes apoptosis, effects that are mediated by Activin Receptor-Like Kinase 2 (ALK2) type I receptor.
conclusionsWe identify BMP9 as a negative regulator of oval cell expansion in cholestatic injury, its deletion enhancing liver regeneration. Likewise, our work further supports BMP9 as an attractive therapeutic target for chronic liver diseases.
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