期刊
DEVELOPMENTAL DYNAMICS
卷 235, 期 1, 页码 82-93出版社
WILEY
DOI: 10.1002/dvdy.20629
关键词
development; chick; epicardium; epithelial-mesenchymal transformation; smooth muscle; transforming growth factor beta receptors
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL052922, P01HL067105] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007347] Funding Source: NIH RePORTER
- NHLBI NIH HHS [P01 HL067105-019001, R01 HL052922-10, HL67105, R01 HL052922, P01 HL067105-010002, P01 HL067105] Funding Source: Medline
- NIGMS NIH HHS [5 T32 GM07347] Funding Source: Medline
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 (TGF beta) stimulates EMT and smooth muscle differentiation of epicardial cells. In epicardial explants, TGF beta 1 and TGF beta 2 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 TGF beta, whereas only inhibition of p160 rho kinase blocked TGF beta-stimulated caldesmon expression. These data demonstrate that TGF beta stimulates loss of epithelial character and smooth muscle differentiation in epicardial cells by means of a mechanism that requires ALK5 and p160 rho kinase.
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