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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)59-64
Number of pages6
JournalInternational journal of molecular medicine
Issue number1
Publication statusPublished - Jul 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics


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