Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats.

Satoru Tsuruta, Makoto Nakamuta, Munechika Enjoji, Kazuhiro Kotoh, Kenichi Hiasa, Kensuke Egashira, Hajime Nawata

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Monocyte chemoattractant protein-1 (MCP-1) has been implicated in the process of hepatic inflammation, recruiting monocytes and lymphocytes during liver injury. MCP-1 also activates directly hepatic stellate cells, which play a major role in hepatic fibrosis. However, it remains unclear whether blockage of MCP-1 signaling could prevent hepatic fibrosis in vivo. We evaluated a strategy for anti-MCP-1 gene therapy against hepatic fibrosis by transfecting an amino-terminal deletion mutant, lacking the amino-terminal codons 2 to 8 of the human MCP-1 gene and designated 7ND, into skeletal muscle in a rat experimental model of dimethylnitrosamine (DMN)-induced fibrosis. Anti-MCP-1 gene therapy decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline contents of the liver, accompanied by a reduction in the expressions of alpha-smooth muscle actin. This treatment also caused a significant decrease in hepatic tissue 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 MCP-1 after intramuscular transfer of the 7ND gene suppressed hepatic fibrosis, and this strategy may be a useful and feasible gene therapy against hepatic fibrosis.

Original languageEnglish
Pages (from-to)837-842
Number of pages6
JournalInternational journal of molecular medicine
Volume14
Issue number5
DOIs
Publication statusPublished - Nov 2004

All Science Journal Classification (ASJC) codes

  • Genetics

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