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Smad protein and TGF-β signaling in vascular smooth muscle cells

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Transforming growth factor-β1 (TGF-β1) plays a role in vascular remodeling by stimulating vascular smooth muscle cell (SMC) growth and matrix-protein synthesis at sites of vascular injury. Smad proteins have been shown to mediate intracellular signaling of this growth factor. We investigated the expression and phosphorylation of Smads in cultured rat aortic smooth muscle cells. In addition, we evaluated the effects of overexpression of Smad proteins on TGF-β signal transduction by adenovirus-mediated gene transfer. In rat SMC, Smad1, Smad2, Smad3, Smad4 and Smad5 were detected by immunoprecipitation. Using antisera against phosphorylated Smad2, we showed that TGF-β1-induced Smad2 phosphorylation in a concentration- and time-dependent manner. Using adenovirus-mediated transfection method, we demonstrated that overexpression of Smad2 or Smad4 was associated with an increased production of TGF-β1-induced plasminogen activator inhibitor-1 (PAI-1). However, the most prominent expression of PAI-1 was observed upon cotransfection of both Smad2 and Smad4. Both the proliferative effect of TGF-β1 under serum-free conditions and its anti-proliferative effect under serum-rich conditions were suppressed by the adenovirus-mediated overexpression of Smad7. These results indicated that Smads proteins were expressed in vascular SMC and that they mediated TGF-β signaling in those cells.
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Document Type: Research Article

Affiliations: Department of Nephrology, Kurume University, School of Medicine, Kurume, Japa

Publication date: May 1, 2003

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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