ArticleExperimental cell research2010
TGFβ2-mediated production of hyaluronan is important for the induction of epicardial cell differentiation and invasion.
Article in Experimental cell research, 2010. 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, 45 citations in OpenAlex.
- DNA Methylation and Fetal Programming of Cardiovascular Disease: From Congenital Heart Diseases to Adult Cardiovascular Dysfunction.Reviews in cardiovascular medicine · 2026Review
- Cardiac EndMT and EpiMT as a developmental continuum: integration of mechanical, metabolic, and epigenetic regulation.Frontiers in cell and developmental biology · 2026Review
- BubR1 Controls Heart Development by Promoting Expression of Cardiogenesis Regulators.Journal of the American Heart Association · 2025Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- Hyaluronic acid-mediated epithelial-mesenchymal transition of human lens epithelial cells via CD44 and TGF-β2.Arquivos brasileiros de oftalmologia · 2024Article
- CCBE1 Is Essential for Epicardial Function during Myocardium Development.International journal of molecular sciences · 2022Article
- Regulation of Epicardial Cell Fate during Cardiac Development and Disease: An Overview.International journal of molecular sciences · 2022Review
- Bioengineering strategies to control epithelial-to-mesenchymal transition for studies of cardiac development and disease.APL bioengineering · 2021Review
- 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
- Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis.Journal of cardiovascular development and disease · 2021Review
- Epicardial Contribution to the Developing and Injured Heart: Exploring the Cellular Composition of the Epicardium.Frontiers in cardiovascular medicine · 2021Review
- Epicardial TGFβ and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?Biomolecules · 2020Review
- Epicardium in Heart Development.Cold Spring Harbor perspectives in biology · 2020Review
- The Role of the Epicardium During Heart Development and Repair.Circulation research · 2020Review
- Altered haemodynamics causes aberrations in the epicardium.Journal of anatomy · 2019Article
- TETs Regulate Proepicardial Cell Migration through Extracellular Matrix Organization during Zebrafish Cardiogenesis.Cell reports · 2019Article
- More than Just a Simple Cardiac Envelope; Cellular Contributions of the Epicardium.Frontiers in cell and developmental biology · 2017Review
- Article
- Common pathways regulate Type III TGFβ receptor-dependent cell invasion in epicardial and endocardial cells.Cellular signalling · 2016Article
- BMP2 rescues deficient cell migration in Tgfbr3(-/-) epicardial cells and requires Src kinase.Cell adhesion & migration · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In the developing heart, the epicardium is a major source of progenitor cells that contribute to the formation of the coronary vessel system. These epicardial progenitors give rise to the different cellular components of the coronary vasculature by undergoing a number of morphological and physiological changes collectively known as epithelial to mesenchymal transformation (EMT). However, the specific signaling mechanisms that regulate epicardial EMT are yet to be delineated. In this study we investigated the role of TGFβ2 and hyaluronan (HA) during epicardial EMT and how signals from these two molecules are integrated during this important process. Here we show that TGFβ2 induces MEKK3 activation, which in turn promotes ERK1/2 and ERK5 phosphorylation. TGFβ2 also increases Has2 expression and subsequent HA production. Nevertheless, inhibition of MEKK3 kinase activity, silencing of ERK5 or pharmacological disruption of ERK1/2 activation significantly abrogates this response. Thus, TGFβ2 promotes Has2 expression and HA production through a MEKK3/ERK1/2/5-dependent cascade. Furthermore, TGFβ2 is able to induce epicardial cell invasion and differentiation but not proliferation. However, inhibition of MEKK3-dependent pathways, degradation of HA by hyaluronidases or blockade of CD44, significantly impairs the biological response to TGFβ2. Taken together, these findings demonstrate that TGFβ2 activation of MEKK3/ERK1/2/5 signaling modulates Has2 expression and HA production leading to the induction of EMT events. This is an important and novel mechanism showing how TGFβ2 and HA signals are integrated to regulate changes in epicardial cell behavior.
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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.