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>
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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