摘要
Background In addition to hematopoietic effect, the erythropoietin is known as a multifunctional cytokine with anti-fibrosis and organ-protective activities. The purpose of this study was to evaluate the effect of recombinant human erythropoietin （rhEPO） on hepatic fibrosis and hepatic stellate cells （HSCs）. Methods Carbon tetrachloride （CCI4） induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study. CCI4 and rhEPO （0,200 or 1000 U/kg） was injected intraperitoneally in BALB/c mice three times a week for 4 weeks. Immunohistochemistry and immunoblotting were performed to evaluate expressions of transforming growth factor-β1 （TGF-β1）, α-smooth muscle actin （α-SMA）, and fibronectin in explanted liver. Immunoblotting of α-SMA, phophorylated Smad-2 and Smad-2/3 was performed in HSCs treated with TGF-β1 and/or rhEPO. Results Expressions of TGF-β1, α-SMA, and fibronectin were increased in CCI4 injected mice livers, but significantly attenuated by co-treatment with CCI4 and rhEPO. Co-treatment of rhEPO markedly suppressed fibrosis in Masson＇s trichrome compared with treatment of only CCI4. TGF-β1 increased phosphorylated α-SMA, Smad-2 expressions in HSCs, which were decreased by rhEPO co-treatment. Conclusions Treatment of rhEPO effectively suppressed fibrosis in CCI4-induced liver fibrosis mice models. Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.
Background In addition to hematopoietic effect, the erythropoietin is known as a multifunctional cytokine with anti-fibrosis and organ-protective activities. The purpose of this study was to evaluate the effect of recombinant human erythropoietin （rhEPO） on hepatic fibrosis and hepatic stellate cells （HSCs）. Methods Carbon tetrachloride （CCI4） induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study. CCI4 and rhEPO （0,200 or 1000 U/kg） was injected intraperitoneally in BALB/c mice three times a week for 4 weeks. Immunohistochemistry and immunoblotting were performed to evaluate expressions of transforming growth factor-β1 （TGF-β1）, α-smooth muscle actin （α-SMA）, and fibronectin in explanted liver. Immunoblotting of α-SMA, phophorylated Smad-2 and Smad-2/3 was performed in HSCs treated with TGF-β1 and/or rhEPO. Results Expressions of TGF-β1, α-SMA, and fibronectin were increased in CCI4 injected mice livers, but significantly attenuated by co-treatment with CCI4 and rhEPO. Co-treatment of rhEPO markedly suppressed fibrosis in Masson＇s trichrome compared with treatment of only CCI4. TGF-β1 increased phosphorylated α-SMA, Smad-2 expressions in HSCs, which were decreased by rhEPO co-treatment. Conclusions Treatment of rhEPO effectively suppressed fibrosis in CCI4-induced liver fibrosis mice models. Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.
