ArticleCellular signalling2012
TGFβ and BMP-2 regulate epicardial cell invasion via TGFβR3 activation of the Par6/Smurf1/RhoA pathway.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 57 citations in OpenAlex.
- Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation.Journal of pharmaceutical analysis · 2026Review
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024Review
- Smurf1 regulates ameloblast polarization by ubiquitination-mediated degradation of RhoA.Cell proliferation · 2023Article
- CCBE1 Is Essential for Epicardial Function during Myocardium Development.International journal of molecular sciences · 2022Article
- ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis.Life science alliance · 2022Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells.NPJ Regenerative medicine · 2022Article
- Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease.Journal of cardiovascular development and disease · 2021Review
- Up-regulation of TβRIII facilitates the osteogenesis of supraspinous ligament-derived fibroblasts from patients with ankylosing spondylitis.Journal of cellular and molecular medicine · 2021Article
- Article
- Epicardial TGFβ and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?Biomolecules · 2020Review
- GDF11 contributes to hepatic hepcidin (HAMP) inhibition through SMURF1-mediated BMP-SMAD signalling suppression.British journal of haematology · 2020Article
- Mesothelium and Malignant Mesothelioma.Journal of developmental biology · 2019Review
- Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk.PLoS genetics · 2018Article
- ΔNp63α Suppresses TGFB2 Expression and RHOA Activity to Drive Cell Proliferation in Squamous Cell Carcinomas.Cell reports · 2018Article
- The E3 ubiquitin ligase SMURF1 regulates cell-fate specification and outflow tract septation during mammalian heart development.Scientific reports · 2018Article
- Hypoxia Supports Epicardial Cell Differentiation in Vascular Smooth Muscle Cells through the Activation of the TGFβ Pathway.Journal of cardiovascular development and disease · 2018Article
- Smurf1 inhibits integrin activation by controlling Kindlin-2 ubiquitination and degradation.The Journal of cell biology · 2017Article
- BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF-β receptor type I ALK5.PloS one · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Coronary vessel development requires transfer of mesothelial cells to the heart surface to form the epicardium where some cells subsequently undergo epithelial-mesenchymal transformation (EMT) and invade the subepicardial matrix. Tgfbr3(-/-) mice die due to failed coronary vessel formation associated with decreased epicardial cell invasion but the mediators downstream of TGFβR3 are not well described. TGFβR3-dependent endocardial EMT stimulated by either TGFβ2 or BMP-2 requires activation of the Par6/Smurf1/RhoA 1pathway where Activin Receptor Like Kinase (ALK5) signals Par6 to act downstream of TGFβ to recruit Smurf1 to target RhoA for degradation to regulate apical-basal polarity and tight junction dissolution. Here we asked if this pathway was operant in epicardial cells and if TGFβR3 was required to access this pathway. Targeting of ALK5 in Tgfbr3(+/+) cells inhibited loss of epithelial character and invasion. Overexpression of wild-type (wt) Par6, but not dominant negative (dn) Par6, induced EMT and invasion while targeting Par6 by siRNA inhibited EMT and invasion. Overexpression of Smurf1 and dnRhoA induced loss of epithelial character and invasion. Targeting of Smurf1 by siRNA or overexpression of constitutively active (ca) RhoA inhibited EMT and invasion. In Tgfbr3(-/-) epicardial cells which have a decreased ability to invade collagen gels in response to TGFβ2, overexpression of wtPar6, Smurf1, or dnRhoA had a diminished ability to induce invasion. Overexpression of TGFβR3 in Tgfbr3(-/-) cells, followed by siRNA targeting of Par6 or Smurf1, diminished the ability of TGFβR3 to rescue invasion demonstrating that the Par6/Smurf1/RhoA pathway is activated downstream of TGFβR3 in epicardial cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.