ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
BMP4 is a novel paracrine inhibitor of liver regeneration.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Pharmacological and toxicological insights into the ayurvedic formulation Rasasindura.Scientific reports · 2025Article
- A spatiotemporal atlas of mouse liver homeostasis and regeneration.Nature genetics · 2024Article
- Review
- Magnesium and Liver Metabolism Through the Lifespan.Advances in nutrition (Bethesda, Md.) · 2023Review
- Review
- BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration.International journal of molecular sciences · 2017Review
- Bone morphogenetic protein signaling governs biliary-driven liver regeneration in zebrafish through tbx2b and id2a.Hepatology (Baltimore, Md.) · 2017Article
- Transforming growth factor-β in liver cancer stem cells and regeneration.Hepatology communications · 2017Review
- Dicer-dependent production of microRNA221 in hepatocytes inhibits p27 and is required for liver regeneration in mice.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Novel transcriptome assembly and comparative toxicity pathway analysis in mahi-mahi (Coryphaena hippurus) embryos and larvae exposed to Deepwater Horizon oil.Scientific reports · 2017Article
- Liver Regeneration: Analysis of the Main Relevant Signaling Molecules.Mediators of inflammation · 2017Review
- Effect of Secreted Molecules of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells on Acute Hepatic Failure Model.Stem cells and development · 2016Article
- SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration.The Journal of biological chemistry · 2016Article
- Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration.The Journal of pharmacology and experimental therapeutics · 2014Article
- Identification of genes in HepG2 cells that respond to DNA methylation and histone deacetylation inhibitor treatment.Experimental and therapeutic medicine · 2014Article
- Potential roles of bone morphogenetic protein (BMP)-9 in human liver diseases.International journal of molecular sciences · 2014Review
- Paracrine signals from liver sinusoidal endothelium regulate hepatitis C virus replication.Hepatology (Baltimore, Md.) · 2014Article
- Intestinal mucosal barrier is injured by BMP2/4 via activation of NF-κB signals after ischemic reperfusion.Mediators of inflammation · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Transforming growth factor (TGF)-β family members exert strong effects on restoration of liver mass after injury. Bone morphogenetic proteins (BMPs) are members of the TGF-β family and are found in the liver, suggesting that these proteins may play a role in liver regeneration. We examined BMP signaling in the liver during hepatectomy. We found that BMP4 is constitutively expressed in the peribiliary stroma and endothelial cells of the liver and that expression is decreased after hepatectomy. Mice driven to maintain BMP4 expression in the liver display inhibited hepatocyte proliferation and restoration of liver mass after hepatectomy, suggesting that reduced BMP4 is necessary for normal regeneration. Consistent with this finding, hepatocyte-specific deletion of the BMP receptor activin receptor-like kinase 3 (Alk3) enhances regeneration and reduces phosphorylation of SMAD1/5/8, a transducer of BMP signaling. In contrast to experiments in wild-type mice, maintaining BMP4 levels has no effect on liver regeneration in hepatocyte-specific Alk3 null mice, providing evidence that BMP4 signals through Alk3 to inhibit liver regeneration. Consistent with these findings, the BMP4 antagonist Noggin enhances regeneration. Furthermore, high-dose BMP4 inhibits proliferation of primary hepatocytes and HepG2 cells in culture. These findings elucidate a new, potentially clinically relevant paradigm in which a constitutively expressed paracrine inhibitory factor plays a critical role in liver regeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.