Erythropoietin decreases carbon tetrachloride-induced hepatic fibrosis by inhibiting transforming growth factor-beta

作     者：Soo Young Park Joo Young Lee Won Young Tak Young Oh Kweon Mi Suk Lee 

作者机构：Department of Internal Medicine Liver Research Institute Graduate School of Medicine Kyungpook National University Daegu Korea 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2012年第125卷第17期

页      面：3098-3103页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 10[医学] 

基　　金：This study was supported by a grant from the 2007 KASL Research Fund 

主　　题：fibrosis erythropoietin transforming growth factor-beta hepatic stellate cell animal model 

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.