ArticleLaboratory investigation; a journal of technical methods and pathology2018
BMP-2 restoration aids in recovery from liver fibrosis by attenuating TGF-β1 signaling.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Palmitoleic acid promoted by BMPR2 signaling primes CD169 macrophages and alleviates liver fibrosis.Communications biology · 2026Article
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- Divergent immune and extracellular matrix transcriptional programs underlie poor prognosis in early-stage lung adenocarcinoma.Frontiers in immunology · 2026Article
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- Modulation of phosphatase of regenerating liver-1 within placental mesenchymal stem cells instigates the transition between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition subsequent to hepatic fibrosis.Clinical and molecular hepatology · 2025Article
- Restoring Prostacyclin/PGI2-PTGIR signaling alleviates intestinal fibrosis in Crohn's disease via fibroblast-specific YAP/TAZ inhibition.Journal of Crohn's & colitis · 2025Article
- Role of mitogens in normal and pathological liver regeneration.Hepatology communications · 2025Review
- Inhibition of RAC1 activator DOCK2 ameliorates cholestatic liver injury via regulating macrophage polarisation and hepatic stellate cell activation.Biology direct · 2025Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Cannabidiol (CBD) modulates the transcriptional profile of ethanol-exposed human dermal fibroblast cells.Journal of applied genetics · 2024Article
- Molecular Interplay in Cardiac Fibrosis: Exploring the Functions of RUNX2, BMP2, and Notch.Reviews in cardiovascular medicine · 2024Review
- miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression.JCI insight · 2024Article
- Roles of transforming growth factor-β signaling in liver disease.World journal of hepatology · 2024Article
- The Influence of Betulin Derivatives EB5 and ECH147 on the Expression of Selected TGFβ Superfamily Genes,Current issues in molecular biology · 2023Article
- NBL1 Reduces Corneal Fibrosis and Scar Formation after Wounding.Biomolecules · 2023Article
- Growth differentiation factor 7 autocrine signaling promotes hepatic progenitor cell expansion in liver fibrosis.Stem cell research & therapy · 2023Article
- Dynamic alterations in metabolomics and transcriptomics associated with intestinal fibrosis in a 2,4,6-trinitrobenzene sulfonic acid-induced murine model.Journal of translational medicine · 2023Article
- Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS/MAPK Signal Activity.International journal of molecular sciences · 2023Article
- Human dental pulp stem cells (hDPSCs) promote the lipofibroblast transition in the early stage of a fibro-inflammatory process.Frontiers in cell and developmental biology · 2023Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) plays a central role in hepatic fibrogenesis. This study investigated the function and mechanism of bone morphogenetic protein-2 (BMP-2) in regulation of hepatic fibrogenesis. BMP-2 expression in fibrotic liver was measured in human tissue microarray and mouse models of liver fibrosis induced by bile duct ligation surgery or carbon tetrachloride administration. Adenovirus-mediated BMP-2 gene delivery was used to test the prophylactic effect on liver fibrosis. Primary hepatic stellate cells (HSC), HSC-T6 and clone-9 cell lines were used to study the interplay between BMP-2 and TGF-β1. Hepatic BMP-2 was localized in parenchymal hepatocytes and activated HSCs and significantly decreased in human and mouse fibrotic livers, showing an opposite pattern of hepatic TGF-β1 contents. BMP-2 gene delivery alleviated the elevations of serum hepatic enzymes, cholangiocyte marker CK19, HSC activation markers, and liver fibrosis in both models. Mechanistically, exogenous TGF-β1 dose dependently reduced BMP-2 expression, whereas BMP-2 significantly suppressed expression of TGF-β and its cognate type I and II receptor peptides, as well as the induced Smad3 phosphorylation levels in primary mouse HSCs. Aside from its suppressive effects on cell proliferation and migration, BMP-2 treatment prominently attenuated the TGF-β1-stimulated α-SMA and fibronectin expression, and reversed the TGF-β1-modulated epithelial-to-mesenchymal transition marker expression in mouse HSCs. The mutual regulation between BMP-2 and TGF-β1 signaling axes may constitute the anti-fibrogenic mechanism of BMP-2 in the pathogenesis of liver fibrosis. BMP-2 may potentially serve as a novel therapeutic target for treatment of liver fibrosis.
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