Downregulation of type I collagen expression in silibinin-treated human skin fibroblasts by blocking the activation of Smad2/3-dependent signaling pathways: Potential therapeutic use in the chemoprevention of keloids
| Autor: | Kwon-Jun Il, Kyu-Suk Lee, Jae-We Cho |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cell
Down-Regulation Silibinin Smad Proteins Smad2 Protein Matrix metalloproteinase Biology Chemoprevention Collagen Type I Transforming Growth Factor beta1 chemistry.chemical_compound Downregulation and upregulation Genetics medicine Humans Smad3 Protein Phosphorylation Promoter Regions Genetic Cell Proliferation Skin Cell Nucleus Tissue Inhibitor of Metalloproteinase-1 Cell Death Oncogene General Medicine Fibroblasts Matrix Metalloproteinases Cell biology medicine.anatomical_structure chemistry Apoptosis Keloid Silybin Signal transduction Type I collagen Signal Transduction Silymarin |
| Zdroj: | International Journal of Molecular Medicine. 31:1148-1152 |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2013.1303 |
| Popis: | The inhibition of the Smad2/3 pathway is a key step involved in the downregulation of type I collagen synthesis, thus preventing keloid formation in tissue. In this study, we investigated the effect of silibinin on the proliferation of human skin fibroblasts (HSFs), as well as its effect on the expression of type I collagen, matrix metalloproteinase (MMP)-1, Smad2 and Smad3. Our results showed that the proliferation rates of the fibroblasts were not markedly decreased in a dose- and time-dependent manner following treatment with silibinin. Even though silibinin did not exert any cytotoxic effects on HSFs, the expression of type I collagen was markedly decreased in a dose- and time-dependent manner in the silibinin-treated HSFs. Consistent with this finding, the decreased promoter activity of type I collagen was observed in the HSFs following treatment with silibinin. The MMP-1 and MMP-2 expression levels were increased in the silibinin-treated HSFs. Moreover, the silibinin-induced downregulation of type I collagen was associated with the inhibition of Smad2/3 activation in the transforming growth factor‑β1 (TGF-β1)-treated HSFs. We further demonstrated that silibinin attenuated the translocation of Smad2 and Smad3 to the nucleus in the TGF-β1-treated HSFs. Taken together, our data indicate that silibinin has the potential to prevent fibrotic skin changes by inducing the downregulation of type I collagen expression; this effect was partly mediated by the inhibition of the Smad2/3-dependent signaling pathway in HSFs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|