![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication August 1, 2005.
Revised November 14, 2005.
Accepted for publication November 15, 2005.
1-Induced Extracellular Matrix Expression
This is the first report that characterizes SIS3 as a potent and selective inhibitor of Smad3 function. In the reporter assay, the increased luciferase activity of p3TP-lux by the overexpression of constitutively active form of ALK-5 was abrogated by the treatment with SIS3 in a dose-dependent manner. Immunoprecipitation revealed that SIS3 attenuated the TGF-
1-induced phosphorylation of Smad3 and interaction of Smad3 with Smad4. On the other hand, the phosphorylation of Smad2 was not affected by this reagent. Subsequently, we evaluated the ability of SIS3 in the suppression of the TGF-1-induced type I procollagen up-regulation in human dermal fibroblasts. We found that the addition of SIS3 attenuated the effects of TGF-1 by reducing the transcriptional activity. SIS3 also inhibited the myofibroblast differentiation of fibroblasts by TGF-1. Moreover, we demonstrated that SIS3 completely diminished the constitutive phosphorylation of Smad3 as well as the up-regulated type I collagen expression in scleroderma fibroblasts. Taken together, our study suggested that SIS3 is a useful tool to evaluate the TGF--regulated cellular mechanisms via selective inhibition of Smad3.
Key words:
Transcriptional coactivators, DNA binding sites, Promoter analysis
This article has been cited by other articles:
|
|
 |
|
  J. B. Samon, A. Champhekar, L. M. Minter, J. C. Telfer, L. Miele, A. Fauq, P. Das, T. E. Golde, and B. A. Osborne Notch1 and TGF{beta}1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells Blood, September 1, 2008; 112(5): 1813 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Shan, T.-p. Yao, H. T. Nguyen, Y. Zhuo, D. R. Levy, R. C. Klingsberg, H. Tao, M. L. Palmer, K. N. Holder, and J. A. Lasky Requirement of HDAC6 for Transforming Growth Factor-{beta}1-induced Epithelial-Mesenchymal Transition J. Biol. Chem., July 25, 2008; 283(30): 21065 - 21073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. B. Li, H. D. Kollias, and K. R. Wagner Myostatin Directly Regulates Skeletal Muscle Fibrosis J. Biol. Chem., July 11, 2008; 283(28): 19371 - 19378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ivanova, M. J. Butt, and D. G. Matsell Mesenchymal transition in kidney collecting duct epithelial cells Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1238 - F1248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Jeon, H. J. Moon, M. J. Lee, H. Y. Song, Y. M. Kim, M. Cho, D.-S. Suh, M.-S. Yoon, C. L. Chang, J. S. Jung, et al. Cancer-Derived Lysophosphatidic Acid Stimulates Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells Stem Cells, March 1, 2008; 26(3): 789 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Le, J. Y. Cho, M. Miller, S. McElwain, K. Golgotiu, and D. H. Broide Inhibition of Allergen-Induced Airway Remodeling in Smad 3-Deficient Mice J. Immunol., June 1, 2007; 178(11): 7310 - 7316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sturrock, T. P. Huecksteadt, K. Norman, K. Sanders, T. M. Murphy, P. Chitano, K. Wilson, J. R. Hoidal, and T. P. Kennedy Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1543 - L1555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bobik Transforming Growth Factor-{beta}s and Vascular Disorders Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1712 - 1720. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
