ArticleAtherosclerosis2011
HGF/c-Met signalling promotes Notch3 activation and human vascular smooth muscle cell osteogenic differentiation in vitro.
Article in Atherosclerosis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
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- Serum proteomic profiling reveals potential predictive indicators for coronary artery calcification in stable ischemic heart disease.Journal of molecular histology · 2025Article
- Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.Circulation research · 2025Article
- Research Progress on the Osteogenesis-Related Regulatory Mechanisms of Human Umbilical Cord Mesenchymal Stem Cells.Stem cell reviews and reports · 2023Review
- Hepatocyte growth factor is associated with greater risk of extracoronary calcification: results from the multiethnic study of atherosclerosis.Open heart · 2022Article
- The two facets of receptor tyrosine kinase in cardiovascular calcification-can tyrosine kinase inhibitors benefit cardiovascular system?Frontiers in cardiovascular medicine · 2022Review
- Resveratrol Ameliorates Aortic Calcification in Ovariectomized Rats via SIRT1 Signaling.Current issues in molecular biology · 2021Article
- The modulatory role of sulfated and non-sulfated small molecule heparan sulfate-glycomimetics in endothelial dysfunction: absolute structural clarification, molecular docking and simulated dynamics, SAR analyses and ADMET studies.RSC medicinal chemistry · 2021Article
- HGF/c-Met signaling regulates early differentiation of placental trophoblast cells.The Journal of reproduction and development · 2021Article
- Loss of SIRT1 in diabetes accelerates DNA damage-induced vascular calcification.Cardiovascular research · 2021Article
- A novel bispecific c-MET/CTLA-4 antibody targetting lung cancer stem cell-like cells with therapeutic potential in human non-small-cell lung cancer.Bioscience reports · 2019Article
- Suppression of SIRT1 in Diabetic Conditions Induces Osteogenic Differentiation of Human Vascular Smooth Muscle Cells via RUNX2 Signalling.Scientific reports · 2019Article
- Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).Atherosclerosis · 2018Article
- The Interplay of SIRT1 and Wnt Signaling in Vascular Calcification.Frontiers in cardiovascular medicine · 2018Review
- Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.Genes · 2017Article
- RANKL-OPG and RAGE modulation in vascular calcification and diabetes: novel targets for therapy.Diabetologia · 2014Review
- Regulatory circuits controlling vascular cell calcification.Cellular and molecular life sciences : CMLS · 2013Review
- Attenuation of chondrogenic transformation in vascular smooth muscle by dietary quercetin in the MGP-deficient mouse model.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesVascular calcification is a major clinical problem and elucidating the underlying mechanism is important to improve the prognosis of patients with cardiovascular disease. We aimed to elucidate the role and mechanism of action of Hepatocyte Growth Factor (HGF)/c-Met signalling in vascular calcification and establish whether blocking this pathway could prevent mineralisation of vascular smooth muscle cells (VSMCs) in vitro. METHODS AND
resultsWe demonstrate increased HGF secretion and c-Met up-regulation and phosphorylation during VSMC osteogenic differentiation. Adenoviral-mediated over-expression of HGF (AdHGF) in VSMCs accelerated mineralisation, shown by alizarin red staining, and significantly increased (45)Calcium incorporation (1.96 ± 0.54-fold [P < 0.05]) and alkaline phosphatase (ALP) activity (3.01 ± 0.8-fold [P < 0.05]) compared to controls. AdHGF also significantly elevated mRNA expression of bone-related proteins, Runx2, osteocalcin, BMP2 and osterix in VSMCs. AdHGF-accelerated mineralisation correlated with increased Akt phosphorylation, nuclear translocation of Notch3 intracellular domain (N3IC) and up-regulation of the Notch3 target protein, HES1. In contrast, adenoviral-mediated over-expression of the HGF antagonist, NK4, markedly attenuated VSMC mineralisation, and reduced c-Met phosphorylation, Akt activation and HES1 protein expression compared to AdHGF-treated cells. Furthermore, the Notch inhibitor, DAPT, attenuated N3IC nuclear translocation and AdHGF-induced mineralisation.
conclusionWe demonstrate HGF induces VSMC osteogenic differentiation via c-Met/Akt/Notch3 signalling, highlighting these pathways as potential targets for intervention of vascular calcification.
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