ArticleThe Journal of clinical investigation2011
Matrix Gla protein deficiency causes arteriovenous malformations in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 94 citations in OpenAlex.
- Molecular mechanisms, therapeutic strategies, and inter-organ fibrosis crosstalk of Gla proteins in cardiovascular disease.Communications biology · 2026Review
- Matrix Gla Protein Expression in Pericytes and Myofibroblasts Contributes to Renal Fibrosis.The American journal of pathology · 2026Article
- Arterial-Lymphatic-Like Endothelial Cells Appear in Hereditary Hemorrhagic Telangiectasia 2 and Contribute to Vascular Leakage and Arteriovenous Malformations.Circulation · 2025Article
- Molecular signatures of alveolar type II cell differentiation in acute respiratory distress syndrome.Frontiers in medicine · 2025Article
- New perspectives on the progression of pulmonary fibrosis: the cascade from aberrant microvascular endothelial cell activation to fibrosis.Frontiers in medicine · 2025Review
- Epigenetics enters the stage in vascular malformations.The Journal of clinical investigation · 2024Article
- Inhibition of endothelial histone deacetylase 2 shifts endothelial-mesenchymal transitions in cerebral arteriovenous malformation models.The Journal of clinical investigation · 2024Article
- Article
- Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia.Nature communications · 2023Article
- Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis.The European respiratory journal · 2023Article
- High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes.Blood · 2022Article
- The vascular protective effect of matrix Gla protein during kidney injury.Frontiers in molecular medicine · 2022Review
- Brain arteriovenous malformation in hereditary hemorrhagic telangiectasia: Recent advances in cellular and molecular mechanisms.Frontiers in human neuroscience · 2022Review
- Review of treatment and therapeutic targets in brain arteriovenous malformation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Review
- Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium.International journal of molecular sciences · 2021Article
- Identification of diverse tumor endothelial cell populations in malignant glioma.Neuro-oncology · 2021Article
- Wavelength of a Turing-type mechanism regulates the morphogenesis of meshwork patterns.Scientific reports · 2021Article
- Pronethalol decreases RBPJκ to reduce Sox2 in cerebral arteriovenous malformation.Vascular medicine (London, England) · 2020Article
- Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth.Circulation research · 2020Article
- Overexpression of Activin Receptor-Like Kinase 1 in Endothelial Cells Suppresses Development of Arteriovenous Malformations in Mouse Models of Hereditary Hemorrhagic Telangiectasia.Circulation research · 2020Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Arteriovenous malformations (AVMs) in organs, such as the lungs, intestine, and brain, are characteristic of hereditary hemorrhagic telangiectasia (HHT), a disease caused by mutations in activin-like kinase receptor 1 (ALK1), which is an essential receptor in angiogenesis, or endoglin. Matrix Gla protein (MGP) is an antagonist of BMPs that is highly expressed in lungs and kidneys and is regulated by ALK1. The objective of this study was to determine the role of MGP in the vasculature of the lungs and kidneys. We found that Mgp gene deletion in mice caused striking AVMs in lungs and kidneys, where overall small organ size contrasted with greatly increased vascularization. Mechanistically, MGP deficiency increased BMP activity in lungs. In cultured lung epithelial cells, BMP-4 induced VEGF expression through induction of ALK1, ALK2, and ALK5. The VEGF secretion induced by BMP-4 in Mgp-/- epithelial cells stimulated proliferation of ECs. However, BMP-4 inhibited proliferation of lung epithelial cells, consistent with the increase in pulmonary vasculature at the expense of lung tissue in the Mgp-null mice. Similarly, BMP signaling and VEGF expression were increased in Mgp-/- mouse kidneys. We therefore conclude that Mgp gene deletion is what we believe to be a previously unidentified cause of AVMs. Because lack of MGP also causes arterial calcification, our findings demonstrate that the same gene defect has drastically different effects on distinct vascular beds.
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