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Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada R2H 2A6
We examined the role of the transforming
growth factor (TGF)-
1 signaling inhibitor Smad 7 in
cardiac fibrosis. TGF-
1 (10 ng/ml) was found to increase
cytosolic Smad 7 expression in primary adult rat fibroblasts and induce
rapid nuclear export of exogenous Smad 7 in COS-7 cells. Furthermore,
overexpression of Smad 7 in primary adult fibroblasts was associated
with suppressed collagen type I and III expression. We detected Smad 7, phosphorylated Smad 2, TGF-
type I receptor (T
RI), and
TGF-
1 proteins in postmyocardial infarct (MI) rat
hearts. In 2 and 4 wk post-MI hearts, Smad 7 and T
RI expression were
decreased in scar tissue, whereas TGF-
1 expression was
increased in scar and viable tissue. In the 8 wk post-MI heart, Smad 7 expression was decreased in both scar tissue and myocardium remote to
the infarct scar. Finally, we confirmed that these changes are
paralleled by decreased expression of cytosolic phosphorylated
receptor-regulated Smad 2 in 4-wk viable myocardium and in 2- and 4-wk
infarct scar tissues. Taken together, our data imply that decreased
inhibitory Smad 7 signal in cardiac fibroblasts may play a role in the
pathogenesis of cardiac fibrosis in the post-MI heart.
primary cardiac fibroblasts; transforming growth
factor-
1; experimental heart failure; myocardial
infarction
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