Purpose  

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.

Methods  

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.

Results  

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.

Conclusion  

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