Transforming growth factor-beta induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells.

Compton LA, Potash DA, Mundell NA, Barnett JV
Dev Dyn. 2006 235 (1): 82-93

PMID: 16258965 · DOI:10.1002/dvdy.20629

During embryogenesis, epicardial cells undergo epithelial-mesenchymal transformation (EMT), invade the myocardium, and differentiate into components of the coronary vasculature, including smooth muscle cells. We tested the hypothesis that transforming growth factor-beta (TGFbeta) stimulates EMT and smooth muscle differentiation of epicardial cells. In epicardial explants, TGFbeta1 and TGFbeta2 induce loss of epithelial morphology, cytokeratin, and membrane-associated Zonula Occludens-1 and increase the smooth muscle markers calponin and caldesmon. Inhibition of activin receptor-like kinase (ALK) 5 blocks these effects, whereas constitutively active (ca) ALK5 increases cell invasion by 42%. Overexpression of Smad 3 did not mimic the effects of caALK5. Inhibition of p160 rho kinase or p38 MAP kinase prevented the loss of epithelial morphology in response to TGFbeta, whereas only inhibition of p160 rho kinase blocked TGFbeta-stimulated caldesmon expression. These data demonstrate that TGFbeta stimulates loss of epithelial character and smooth muscle differentiation in epicardial cells by means of a mechanism that requires ALK5 and p160 rho kinase.

2005 Wiley-Liss, Inc.

MeSH Terms (16)

Activin Receptors, Type I Animals Calmodulin-Binding Proteins Cell Differentiation Chick Embryo Epithelium Intracellular Signaling Peptides and Proteins Myocytes, Smooth Muscle Organ Culture Techniques p38 Mitogen-Activated Protein Kinases Pericardium Protein-Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta rho-Associated Kinases Transforming Growth Factor beta

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