Epigallocatechin gallate and genistein attenuate glial fibrillary acidic protein elevation induced by fibrogenic cytokines in hepatic stellate cells

  • Authors:
    • Chunyan Zhang
    • Lang Zhuo
  • View Affiliations

  • Published online on: December 1, 2006     https://doi.org/10.3892/ijmm.18.6.1141
  • Pages: 1141-1151
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Abstract

Hepatic stellate cells (HSCs) play a pivotal role in hepatic fibrogenesis, and are considered a cellular target for therapeutic intervention. We recently established that a 2.2-kb hGFAP (human glial fibrillary acidic protein) promoter could be used to specifically target cultured HSCs. In the current study, we aimed to investigate whether the same transgene (2.2-kb hGFAP-lacZ) can be used as a biomarker for studying the inhibition of HSC activation. HSC-T6 cells stably transfected with the transgene were treated with two natural anti-fibrotic compounds, epigallocatechin gallate (EGCG) and genistein separately. Results showed that both transgenic β-galactosidase activity and endogenous GFAP expression (mRNA and protein) were attenuated by EGCG or genistein treatment in a dose- and time-dependent manner. Our data further demonstrated that the suppression of fibrogenic end-points was primarily mediated through the inhibition of AP-1 signaling (and to a lesser degree through the NFκB pathway) onto the GFAP promoter. In conclusion, the current findings provide a proof-of-concept for using GFAP for studying HSC activation and inhibition. It could be envisioned that a HSC-based high-throughput system can be constructed using the GFAP promoter in conjunction with a real-time reporter for the screening of anti-fibrotic and anti-inflammatory agents.

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December 2006
Volume 18 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang C and Zhuo L: Epigallocatechin gallate and genistein attenuate glial fibrillary acidic protein elevation induced by fibrogenic cytokines in hepatic stellate cells. Int J Mol Med 18: 1141-1151, 2006.
APA
Zhang, C., & Zhuo, L. (2006). Epigallocatechin gallate and genistein attenuate glial fibrillary acidic protein elevation induced by fibrogenic cytokines in hepatic stellate cells. International Journal of Molecular Medicine, 18, 1141-1151. https://doi.org/10.3892/ijmm.18.6.1141
MLA
Zhang, C., Zhuo, L."Epigallocatechin gallate and genistein attenuate glial fibrillary acidic protein elevation induced by fibrogenic cytokines in hepatic stellate cells". International Journal of Molecular Medicine 18.6 (2006): 1141-1151.
Chicago
Zhang, C., Zhuo, L."Epigallocatechin gallate and genistein attenuate glial fibrillary acidic protein elevation induced by fibrogenic cytokines in hepatic stellate cells". International Journal of Molecular Medicine 18, no. 6 (2006): 1141-1151. https://doi.org/10.3892/ijmm.18.6.1141