PMID- 16245329 OWN - NLM STAT- MEDLINE DCOM- 20060317 LR - 20181113 IS - 1058-8388 (Print) IS - 1058-8388 (Linking) VI - 235 IP - 1 DP - 2006 Jan TI - Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium. PG - 50-9 AB - 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. CI - 2005 Wiley-Liss, Inc. FAU - Olivey, Harold E AU - Olivey HE AD - Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600, USA. FAU - Mundell, Nathan A AU - Mundell NA FAU - Austin, Anita F AU - Austin AF FAU - Barnett, Joey V AU - Barnett JV LA - eng GR - T32 GM007628/GM/NIGMS NIH HHS/United States GR - HL076133/HL/NHLBI NIH HHS/United States GR - HL52922/HL/NHLBI NIH HHS/United States GR - HL067105/HL/NHLBI NIH HHS/United States GR - T32 HL076133/HL/NHLBI NIH HHS/United States GR - P01 HL067105-05/HL/NHLBI NIH HHS/United States GR - R01 HL052922-10/HL/NHLBI NIH HHS/United States GR - GM007628/GM/NIGMS NIH HHS/United States GR - R01 HL052922/HL/NHLBI NIH HHS/United States GR - P01 HL067105/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Dev Dyn JT - Developmental dynamics : an official publication of the American Association of Anatomists JID - 9201927 RN - 0 (Membrane Proteins) RN - 0 (Phosphoproteins) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (Smad6 Protein) RN - 0 (Transforming Growth Factor beta) RN - 0 (Zonula Occludens-1 Protein) RN - 104781-85-3 (Fibroblast Growth Factor 1) RN - 126469-10-1 (Fibroblast Growth Factor 7) SB - IM MH - Animals MH - Cell Differentiation/*physiology MH - Chick Embryo MH - Epithelium/*embryology/metabolism MH - Fibroblast Growth Factor 1/physiology MH - Fibroblast Growth Factor 7/physiology MH - Genes, Reporter MH - Membrane Proteins/biosynthesis/genetics/metabolism MH - Mesoderm/cytology/*metabolism MH - Pericardium/cytology/*embryology/metabolism MH - Phosphoproteins/biosynthesis/genetics/metabolism MH - Receptors, Transforming Growth Factor beta/genetics/metabolism MH - Smad6 Protein/biosynthesis/genetics MH - Transforming Growth Factor beta/*physiology MH - Zonula Occludens-1 Protein PMC - PMC3160345 MID - NIHMS69727 EDAT- 2005/10/26 09:00 MHDA- 2006/03/18 09:00 PMCR- 2011/08/23 CRDT- 2005/10/26 09:00 PHST- 2005/10/26 09:00 [pubmed] PHST- 2006/03/18 09:00 [medline] PHST- 2005/10/26 09:00 [entrez] PHST- 2011/08/23 00:00 [pmc-release] AID - 10.1002/dvdy.20593 [doi] PST - ppublish SO - Dev Dyn. 2006 Jan;235(1):50-9. doi: 10.1002/dvdy.20593.