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Int J Mol Med. 2013 May;31(5):1148-52. doi: 10.3892/ijmm.2013.1303. Epub 2013 Mar 14.

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.

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  • 1Department of Dermatology, Keimyung University School of Medicine, Jung-Gu, Daegu 700-712, Republic of Korea.

Abstract

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.

PMID:
23503720
[PubMed - indexed for MEDLINE]
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