Pharmaceutical Research

, Volume 23, Issue 1, pp 82–89 | Cite as

Smad3 Specific Inhibitor, Naringenin, Decreases the Expression of Extracellular Matrix Induced by TGF-β1 in Cultured Rat Hepatic Stellate Cells

  • Xingjun Liu
  • Wei Wang
  • Han Hu
  • Ning Tang
  • Chunling Zhang
  • Wei Liang
  • Minwei Wang
Research Paper


During the process of liver fibrogenesis, transforming growth factor-β (TGF-β) plays an essential role in modulating extracellular matrix (ECM) gene expression, and a growing body of evidence suggests that this is a Smad3-dependent process in the activated hepatic stellate cells (HSCs). Naringenin showed a significantly protective effect on experimental rat liver fibrosis, in our efforts to elucidate its antifibrosis molecular mechanisms and to find a novel target based on Smad3 signaling for challenging fibrosis diseases.


In this study, reverse transcription-polymerase chain reaction and Western blot assays were used to investigate the inhibitory effect of naringenin on ECM formation induced by TGF-β1 in the HSC-T6 cells.


Naringenin reduced not only the accumulation of ECM, including collagen Iα1 (Col Iα1), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1), but also the production of Smad3 induced by TGF-β1 in both mRNA and protein levels in a dose-dependent manner. Moreover, naringenin selectively inhibited the transcription of Smad3, but not other Smads involved in TGF-β1 signaling pathways.


Our data demonstrate that naringenin can exert antifibrogenic effects by directly or indirectly down-regulating Smad3 protein expression and phosphorylation through TGF-β signaling.

Key Words

extracellular matrix liver fibrosis naringenin Smad3 transforming growth factor-1 


Col Iα1

collagen Iα1


Dulbecco's Modified Eagle Medium


extracellular matrix


fetal calf serum




hepatic stellate cells


50% lethal concentration


plasminogen activator inhibitor 1


Tris-buffered saline/Tween 20


transforming growth factor β1


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Xingjun Liu
    • 1
    • 2
  • Wei Wang
    • 1
  • Han Hu
    • 1
  • Ning Tang
    • 1
  • Chunling Zhang
    • 1
  • Wei Liang
    • 1
  • Minwei Wang
    • 2
  1. 1.National Laboratory of Biomacromolecules, Institute of BiophysicsChinese Academy of SciencesBeijingChina
  2. 2.School of PharmacyShenyang Pharmaceutical UniversityShenyangChina

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