Abstract
The proepicardium (PE) migrates over the heart and forms the epicardium. A subset of these PE-derived cells undergoes epithelial-mesenchymal transformation (EMT) and gives rise to cardiac fibroblasts and components of the coronary vasculature. We report that transforming growth factor-beta (TGFbeta) 1 and TGFbeta2 increase EMT in PE explants as measured by invasion into a collagen gel, loss of cytokeratin expression, and redistribution of ZO1. The type I TGFbeta receptors ALK2 and ALK5 are both expressed in the PE. However, only constitutively active (ca) ALK2 stimulates PE-derived epithelial cell activation, the first step in transformation, whereas caALK5 stimulates neither activation nor transformation in PE explants. Overexpression of Smad6, an inhibitor of ALK2 signaling, inhibits epithelial cell activation, whereas BMP7, a known ligand for ALK2, has no effect. These data demonstrate that TGFbeta stimulates transformation in the PE and suggest that ALK2 partially mediates this effect.
2005 Wiley-Liss, Inc.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / physiology*
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Chick Embryo
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Epithelium / embryology*
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Epithelium / metabolism
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Fibroblast Growth Factor 1 / physiology
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Fibroblast Growth Factor 7 / physiology
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Genes, Reporter
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mesoderm / cytology
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Mesoderm / metabolism*
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Pericardium / cytology
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Pericardium / embryology*
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Pericardium / metabolism
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Phosphoproteins / biosynthesis
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism
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Smad6 Protein / biosynthesis
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Smad6 Protein / genetics
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Transforming Growth Factor beta / physiology*
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Zonula Occludens-1 Protein
Substances
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Membrane Proteins
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Phosphoproteins
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Receptors, Transforming Growth Factor beta
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Smad6 Protein
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Transforming Growth Factor beta
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Zonula Occludens-1 Protein
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Fibroblast Growth Factor 1
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Fibroblast Growth Factor 7