ArticleArteriosclerosis, thrombosis, and vascular biology2013
Dkk1 and MSX2-Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020Pooled it
- The miR-335-5p/DKK1/autophagy axis regulates TNF-α-mediated dysfunction of dental pulp stem cells.In vitro cellular & developmental biology. Animal · 2026Article
- M2 macrophages promote heterotopic ossification through MSX2 binding to LEF1-mediated endothelial-mesenchymal transition.Stem cell research & therapy · 2026Article
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Molecular mechanisms of endothelial-mesenchymal transition and its pathophysiological feature in cerebrovascular disease.Cell & bioscience · 2025Review
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications.Angiogenesis · 2024Article
- Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling.International journal of molecular sciences · 2023Review
- Endothelial-to-Mesenchymal Transition: Potential Target of Doxorubicin-Induced Cardiotoxicity.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Review
- Vascular calcification progression and its association with mineral and bone disorder in kidney transplant recipients.Renal failure · 2023Article
- Arterial Stiffness and the Canonical WNT/β-catenin Pathway.Current hypertension reports · 2022Review
- Review
- Endoplasmic Reticulum Stress and Pathogenesis of Vascular Calcification.Frontiers in cardiovascular medicine · 2022Review
- Epithelial-mesenchymal transition-related genes in coronary artery disease.Open medicine (Warsaw, Poland) · 2022Article
- ROS-Influenced Regulatory Cross-Talk With Wnt Signaling Pathway During Perinatal Development.Frontiers in molecular biosciences · 2022Review
- Platelets: Implications in Aortic Valve Stenosis and Bioprosthetic Valve Dysfunction From Pathophysiology to Clinical Care.JACC. Basic to translational science · 2021Review
- Regulation of MDM2 E3 ligase-dependent vascular calcification by MSX1/2.Experimental & molecular medicine · 2021Article
- A promising field: regulating imbalance of EndMT in cardiovascular diseases.Cell cycle (Georgetown, Tex.) · 2021Review
- The complex role of Wnt ligands in type 2 diabetes mellitus and related complications.Journal of cellular and molecular medicine · 2021Review
- Endothelial-to-mesenchymal transition in systemic sclerosis.Clinical and experimental immunology · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveEndothelial cells (ECs) can undergo an endothelial-mesenchymal transition with tissue fibrosis. Wnt- and Msx2-regulated signals participate in arteriosclerotic fibrosis and calcification. We studied the impact of Wnt7, Msx2, and Dkk1, a Wnt7 antagonist, on endothelial-mesenchymal transition in primary aortic ECs. APPROACH AND
resultsTransduction of aortic ECs with vectors expressing Dkk1 suppressed EC differentiation and induced a mineralizing myofibroblast phenotype. Dkk1 suppressed claudin 5, PECAM, cadherin 5 (Cdh5), Tie1, and Tie2. Dkk1 converted the cuboidal cell monolayer into a spindle-shaped multilayer and inhibited EC cord formation. Myofibroblast and osteogenic markers, SM22, type I collagen, Osx, Runx2, and alkaline phosphatase, were upregulated by Dkk1 via activin-like kinase/Smad pathways. Dkk1 increased fibrotic mineralization of aortic ECs cultured under osteogenic conditions--the opposite of mesenchymal cell responses. Msx2 and Wnt7b maintained morphology and upregulated markers of differentiated ECs. Deleting EC Wnt7b with the Cdh5-Cre transgene in Wnt7b(fl/fl);LDLR(-/-) mice upregulated aortic osteogenic genes (Osx, Sox9, Runx2, and Msx2) and nuclear phospho-Smad1/5, and increased collagen and calcium accumulation.
conclusionsDkk1 enhances endothelial-mesenchymal transition in aortic ECs, whereas Wnt7b and Msx2 signals preserve EC phenotype. EC responses to Dkk1, Wnt7b, and Msx2 are the opposite of mesenchymal responses, coupling EC phenotypic stability with osteofibrogenic predilection during arteriosclerosis.
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Registered trials
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