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

Makoto Nakamuta, Shusuke Morizono, Satoru Tsuruta, Motoyuki Kohjima, Kazuhiro Kotoh, Munechika Enjoji

研究成果: ジャーナルへの寄稿記事

13 引用 (Scopus)

抄録

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-betaIIR)] into skeletal muscle in a rat experimental model of dimethylnitrosamine- (DMN-) induced fibrosis. sTGF-betaIIR 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 alpha-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.

元の言語英語
ページ(範囲)59-64
ページ数6
ジャーナルInternational journal of molecular medicine
16
発行部数1
出版物ステータス出版済み - 1 1 2005

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Fibrosis
Muscles
Liver
Transforming Growth Factor beta
Dimethylnitrosamine
Genetic Therapy
Th1-Th2 Balance
Cytokines
transforming growth factor-beta type II receptor
Hepatic Stellate Cells
Hydroxyproline
Interleukin-12
Interleukin-10
Extracellular Matrix
Smooth Muscle
Actins
Skeletal Muscle
Plasmids
Theoretical Models
Collagen

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Remote delivery and expression of soluble type II TGF-beta receptor in muscle prevents hepatic fibrosis in rats. / Nakamuta, Makoto; Morizono, Shusuke; Tsuruta, Satoru; Kohjima, Motoyuki; Kotoh, Kazuhiro; Enjoji, Munechika.

:: International journal of molecular medicine, 巻 16, 番号 1, 01.01.2005, p. 59-64.

研究成果: ジャーナルへの寄稿記事

Nakamuta, Makoto ; Morizono, Shusuke ; Tsuruta, Satoru ; Kohjima, Motoyuki ; Kotoh, Kazuhiro ; Enjoji, Munechika. / Remote delivery and expression of soluble type II TGF-beta receptor in muscle prevents hepatic fibrosis in rats. :: International journal of molecular medicine. 2005 ; 巻 16, 番号 1. pp. 59-64.
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