Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats

被引：10

作者：

Nakamuta, M ^{[1
]}

Morizono, S ^{[1
]}

Tsuruta, S ^{[1
]}

Kohjima, M ^{[1
]}

Kotoh, K ^{[1
]}

Enjoji, M ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2005年 / 16卷 / 01期

关键词：

soluble TGF-beta receptor; type I collagen; Th1/Th2; cytokines; biofactory; intramuscular injection;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Transforming growth factor-beta (TGF-beta) has been implicated in the process of hepatic fibrosis, and stimulates production of extracellular matrix in hepatic stellate cells, which play a major role in the process. It has been recently reported that blockage of TGF-beta signaling prevents hepatic fibrosis. We evaluated a strategy for anti-TGF-beta gene therapy for hepatic fibrosis by transfecting plasmids expressing an entire extracellular domain of human TGF-beta type II [soluble type II TGF-beta receptor (sTGF-beta IIR)] into skeletal muscle in a rat experimental model of dimethylnitrosamine- (DMN-) induced fibrosis. sTGF-beta IIR treatment decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline content of the liver, and reduced the expression of collagen and a-smooth muscle actin. The treatment also caused a significant decrease in hepatic levels of interleukin- (IL-) 12 (Th1 cytokine) and an increase in those of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In conclusion, blockade of TGF-beta after intramuscular transfer of the soluble type II TGF-beta receptor gene suppressed hepatic fibrosis, suggesting that this strategy may be useful for gene therapy of hepatic fibrosis.

引用

页码：59 / 64

页数：6

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