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Erythropoietin decreases carbon tetrachloride-induced hepatic fibrosis by inhibiting transforming growth factor-beta / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 3098-3103, 2012.
Article in English | WPRIM | ID: wpr-316561
ABSTRACT
<p><b>BACKGROUND</b>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).</p><p><b>METHODS</b>Carbon tetrachloride (CCl(4)) induced hepatic fibrosis mice models were used for in vivo study and HSCs line for in vitro study. CCl(4) 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.</p><p><b>RESULTS</b>Expressions of TGF-β1, α-SMA, and fibronectin were increased in CCl(4) injected mice livers, but significantly attenuated by co-treatment with CCl(4) and rhEPO. Co-treatment of rhEPO markedly suppressed fibrosis in Masson's trichrome compared with treatment of only CCl(4). TGF-β1 increased phosphorylated α-SMA, Smad-2 expressions in HSCs, which were decreased by rhEPO co-treatment.</p><p><b>CONCLUSIONS</b>Treatment of rhEPO effectively suppressed fibrosis in CCl(4)-induced liver fibrosis mice models. Anti-fibrosis effect of rhEPO could be related to inhibition of TGF-β1 induced activation of HSCs.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Physiology / Recombinant Proteins / Carbon Tetrachloride / Cells, Cultured / Transforming Growth Factor beta / Erythropoietin / Fibronectins / Therapeutic Uses / Smad2 Protein Type of study: Prognostic study Limits: Animals Language: English Journal: Chinese Medical Journal Year: 2012 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Physiology / Recombinant Proteins / Carbon Tetrachloride / Cells, Cultured / Transforming Growth Factor beta / Erythropoietin / Fibronectins / Therapeutic Uses / Smad2 Protein Type of study: Prognostic study Limits: Animals Language: English Journal: Chinese Medical Journal Year: 2012 Type: Article