PMID- 16258965
OWN - NLM
STAT- MEDLINE
DCOM- 20060317
LR  - 20211203
IS  - 1058-8388 (Print)
IS  - 1058-8388 (Linking)
VI  - 235
IP  - 1
DP  - 2006 Jan
TI  - Transforming growth factor-beta induces loss of epithelial character and smooth 
      muscle cell differentiation in epicardial cells.
PG  - 82-93
AB  - 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.
CI  - 2005 Wiley-Liss, Inc.
FAU - Compton, Leigh A
AU  - Compton LA
AD  - Department of Pharmacology, Vanderbilt University Medical Center, Nashville, 
      Tennessee 37232-6600, USA.
FAU - Potash, Dru A
AU  - Potash DA
FAU - Mundell, Nathan A
AU  - Mundell NA
FAU - Barnett, Joey V
AU  - Barnett JV
LA  - eng
GR  - P01 HL067105-010002/HL/NHLBI NIH HHS/United States
GR  - P01 HL067105-019001/HL/NHLBI NIH HHS/United States
GR  - HL67105/HL/NHLBI NIH HHS/United States
GR  - R01 HL052922-10/HL/NHLBI NIH HHS/United States
GR  - R01 HL052922/HL/NHLBI NIH HHS/United States
GR  - 5 T32 GM07347/GM/NIGMS 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 (Calmodulin-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.30 (Activin Receptors, Type I)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
SB  - IM
MH  - Activin Receptors, Type I/physiology
MH  - Animals
MH  - Calmodulin-Binding Proteins/biosynthesis/genetics
MH  - Cell Differentiation/*physiology
MH  - Chick Embryo
MH  - Epithelium/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Myocytes, Smooth Muscle/*cytology/enzymology/metabolism
MH  - Organ Culture Techniques
MH  - Pericardium/*cytology/enzymology/metabolism
MH  - Protein Serine-Threonine Kinases/physiology
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptors, Transforming Growth Factor beta/physiology
MH  - Transforming Growth Factor beta/*physiology
MH  - p38 Mitogen-Activated Protein Kinases/physiology
MH  - rho-Associated Kinases
EDAT- 2005/11/01 09:00
MHDA- 2006/03/18 09:00
CRDT- 2005/11/01 09:00
PHST- 2005/11/01 09:00 [pubmed]
PHST- 2006/03/18 09:00 [medline]
PHST- 2005/11/01 09:00 [entrez]
AID - 10.1002/dvdy.20629 [doi]
PST - ppublish
SO  - Dev Dyn. 2006 Jan;235(1):82-93. doi: 10.1002/dvdy.20629.