Downregulation of syndecan-1 expression induces activation of hepatic stellate cells via the TGF-β1/Smad3 signaling pathway

Abstract

The activation of hepatic stellate cells (HSCs) is considered associated with liver fibrosis. However, the exact role of syndecan-1 (SDC 1), a protein that regulates the interaction between cells and the microenvironment, in the activation of HSCs resulting in liver fibrosis remains elusive. The objective of the present study was to explore the effects and mechanism of action of SDC1 in the activation of HSCs. HSCs were isolated from mouse liver and cultured to detect the expression of SDC1, transforming growth factor (TGF)-β1, Smad3 and α-smooth muscle actin (α-SMA; a marker of HSC activation) by western blotting and reverse transcription-quantitative PCR. The expression of SDC1 was found to be downregulated, while the expression of TGF-β1, Smad3 and α-SMA was upregulated in HSCs during cell culture. In addition, following stimulation of HSCs with recombinant SDC1, the expression of TGF-β1, Smad3 and α-SMA in HSCs was downregulated, whereas small interfering RNA targeting Smad3 antagonized the effects of recombinant SDC1 on α-SMA. Taken together, these data suggest that SDC1 plays a key role in the development of liver fibrosis.