ArticleDisease models & mechanisms2014
TGF-β mediates early angiogenesis and latent fibrosis in an Emilin1-deficient mouse model of aortic valve disease.
Article in Disease models & mechanisms, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Loss of EMILIN-1/integrin axis drives microenvironmental reprogramming in gastric tumorigenesis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Targeting canonical TGFβ/SMAD3 and ERK1/2 signaling in human valve interstitial cells to modulate immune-fibrotic responses in rheumatic heart disease.Journal of physiology and biochemistry · 2026Article
- Proteomic and degradomic signatures of extracellular matrix remodeling in calcific aortic valve stenosis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Roles and molecular mechanisms of EMILIN-1 in physiology and disease: a narrative review.Frontiers in medicine · 2026Review
- EMILIN-1 in the tumor microenvironment: insights from CNS tumors and beyond.Frontiers in oncology · 2026Review
- The Expanding Genetic Architecture of Arteriopathies: From Canonical TAAD Genes to Emerging Connective Tissue and Signaling Pathways.Medical sciences (Basel, Switzerland) · 2025Review
- Sex-specific response to A1BG loss results in female dilated cardiomyopathy.Biology of sex differences · 2025Article
- Generation of Tailored Extracellular Matrix Hydrogels for the Study of In Vitro Folliculogenesis in Response to Matrisome-Dependent Biochemical Cues.Bioengineering (Basel, Switzerland) · 2024Article
- Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.Cell death & disease · 2023Article
- Single-cell transcriptomics reveals cellular heterogeneity and macrophage-to-mesenchymal transition in bicuspid calcific aortic valve disease.Biology direct · 2023Article
- TGF-beta signal transduction: biology, function and therapy for diseases.Molecular biomedicine · 2022Review
- EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.American journal of human genetics · 2022Article
- miR-491-5p inhibits Emilin 1 to promote fibroblasts proliferation and fibrosis in gluteal muscle contracture via TGF-Beta1/Smad2 pathway.Physiological research · 2022Article
- Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.International journal of molecular sciences · 2022Review
- Pro-inflammatory mediators released by activated monocytes promote aortic valve fibrocalcific activity.Molecular medicine (Cambridge, Mass.) · 2022Article
- Clinical implications of the biomechanics of bicuspid aortic valve and bicuspid aortopathy.Frontiers in cardiovascular medicine · 2022Review
- Review
- Curcumin Suppresses TGF-β1-Induced Myofibroblast Differentiation and Attenuates Angiogenic Activity of Orbital Fibroblasts.International journal of molecular sciences · 2021Article
- Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease.Journal of cardiovascular development and disease · 2021Article
- A role for the MEGF6 gene in predisposition to osteoporosis.Annals of human genetics · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Aortic valve disease (AVD) is characterized by elastic fiber fragmentation (EFF), fibrosis and aberrant angiogenesis. Emilin1 is an elastin-binding glycoprotein that regulates elastogenesis and inhibits TGF-β signaling, but the role of Emilin1 in valve tissue is unknown. We tested the hypothesis that Emilin1 deficiency results in AVD, mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β dysregulation. Using histology, immunohistochemistry, electron microscopy, quantitative gene expression analysis, immunoblotting and echocardiography, we examined the effects of Emilin1 deficiency (Emilin1-/-) in mouse aortic valve tissue. Emilin1 deficiency results in early postnatal cell-matrix defects in aortic valve tissue, including EFF, that progress to latent AVD and premature death. The Emilin1-/- aortic valve displays early aberrant provisional angiogenesis and late neovascularization. In addition, Emilin1-/- aortic valves are characterized by early valve interstitial cell activation and proliferation and late myofibroblast-like cell activation and fibrosis. Interestingly, canonical TGF-β signaling (phosphorylated Smad2 and Smad3) is upregulated constitutively from birth to senescence, whereas non-canonical TGF-β signaling (phosphorylated Erk1 and Erk2) progressively increases over time. Emilin1 deficiency recapitulates human fibrotic AVD, and advanced disease is mediated by non-canonical (MAPK/phosphorylated Erk1 and Erk2) TGF-β activation. The early manifestation of EFF and aberrant angiogenesis suggests that these processes are crucial intermediate factors involved in disease progression and therefore might provide new therapeutic targets for human AVD.
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