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.
机构:
Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, SwedenUniv Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Afrakhte, M
Morén, A
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Morén, A
Jossan, S
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Jossan, S
Itoh, S
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Itoh, S
Westermark, B
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Westermark, B
Heldin, CH
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Heldin, CH
Heldin, NE
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Heldin, NE
ten Dijke, P
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
机构:
THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107
BASHEY, RI
MARTINEZHERNANDEZ, A
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THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107
MARTINEZHERNANDEZ, A
JIMENEZ, SA
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THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107
机构:
Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, SwedenUniv Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Afrakhte, M
Morén, A
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Morén, A
Jossan, S
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Jossan, S
Itoh, S
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Itoh, S
Westermark, B
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h-index: 0
机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Westermark, B
Heldin, CH
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Heldin, CH
Heldin, NE
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机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
Heldin, NE
ten Dijke, P
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h-index: 0
机构:Univ Uppsala Hosp, Dept Genet & Pathol, Pathol Unit, S-75185 Uppsala, Sweden
机构:
THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107
BASHEY, RI
MARTINEZHERNANDEZ, A
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机构:
THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107
MARTINEZHERNANDEZ, A
JIMENEZ, SA
论文数: 0引用数: 0
h-index: 0
机构:
THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107