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

被引:127
作者
Wang, BQ [1 ]
Hao, JM [1 ]
Jones, SC [1 ]
Yee, MS [1 ]
Roth, JC [1 ]
Dixon, IMC [1 ]
机构
[1] Univ Manitoba, St Boniface Gen Hosp, Inst Cardiovasc Sci, Res Ctr, Winnipeg, MB R2H 2A6, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2002年 / 282卷 / 05期
关键词
primary cardiac fibroblasts; transforming growth factor-beta(1); experimental heart failure; myocardial infarction;
D O I
10.1152/ajpheart.00266.2001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (TbetaRI), and TGF-beta(1) proteins in postmyocardial infarct (MI) rat hearts. In 2 and 4 wk post-MI hearts, Smad 7 and TbetaRI 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.
引用
收藏
页码:H1685 / H1696
页数:12
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