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Am J Physiol Heart Circ Physiol 282: H1685-H1696, 2002. First published January 17, 2002; doi:10.1152/ajpheart.00266.2001
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Vol. 282, Issue 5, H1685-H1696, May 2002

Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart

Baiqiu Wang, Jianming Hao, Stephen C. Jones, May-Sann Yee, Julie C. Roth, and Ian M. C. Dixon

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)-beta 1 signaling inhibitor Smad 7 in cardiac fibrosis. TGF-beta 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-beta type I receptor (Tbeta RI), and TGF-beta 1 proteins in postmyocardial infarct (MI) rat hearts. In 2 and 4 wk post-MI hearts, Smad 7 and Tbeta RI expression were decreased in scar tissue, whereas TGF-beta 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-beta 1; experimental heart failure; myocardial infarction


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