Pokeweed antiviral protein down-regulates Wnt/β-catenin signalling to attenuate liver fibrogenesis in vitro and in vivo.

BACKGROUND AND AIM: Pokeweed antiviral protein (PAP) has been regarded as a strong negative regulator of Wnt/β-catenin signalling, which promotes tissue fibrogenesis. Whether PAP inhibits hepatic fibrosis remains unknown. Here, the inhibitory effects of PAP on hepatic fibrosis induced by CCl4 in rats were monitored.

METHODS: Plasmid pXF3H-PAP was transduced into liver in vivo and hepatic stellate cell (HSC-T6) in vitro. Changes in liver pathology were examined by haematoxylin and eosin (H&E) and Masson's trichrome staining. Hepatic function and the levels of hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in liver were measured. We also observed the expressions and distribution of α-SMA, TIMP-1, smad3 and β-catenin in HSCs and liver, together with the viability of HSC-T6 cells.

RESULTS: PAP obviously attenuated the histological changes, decreased the content of Hyp in liver and improved liver function in rats (P<0.05). PAP significantly reduced the expressions and distribution of α-SMA and β-catenin in vivo (0.0125 ± 0.002 vs. 0.0374 ± 0.003, 0.0135 ± 0.003 vs. 0.0382 ± 0.004; P<0.05, respectively) and in vitro as well as the cell viability (P<0.05).

CONCLUSIONS: Our results revealed that PAP attenuated liver fibrogenesis through down-regulating the Wnt/β-catenin pathway. It provides us an alternative new strategy for the treatment of hepatic fibrosis.