PMID- 15492853
OWN - NLM
STAT- MEDLINE
DCOM- 20050531
LR  - 20220227
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 14
IP  - 5
DP  - 2004 Nov
TI  - Anti-monocyte chemoattractant protein-1 gene therapy prevents 
      dimethylnitrosamine-induced hepatic fibrosis in rats.
PG  - 837-42
AB  - 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.
FAU - Tsuruta, Satoru
AU  - Tsuruta S
AD  - Department of Medicine and Bioregulatory Science, Graduate School of Medical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Nakamuta, Makoto
AU  - Nakamuta M
FAU - Enjoji, Munechika
AU  - Enjoji M
FAU - Kotoh, Kazuhiro
AU  - Kotoh K
FAU - Hiasa, Kenichi
AU  - Hiasa K
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Nawata, Hajime
AU  - Nawata H
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Codon)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Chemokine CCL2/*antagonists & inhibitors/*genetics
MH  - Codon/*genetics/*therapeutic use
MH  - Dimethyl Sulfoxide
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Liver Cirrhosis, Experimental/genetics/*therapy
MH  - Male
MH  - Rats
MH  - Rats, Wistar
EDAT- 2004/10/20 09:00
MHDA- 2005/06/01 09:00
CRDT- 2004/10/20 09:00
PHST- 2004/10/20 09:00 [pubmed]
PHST- 2005/06/01 09:00 [medline]
PHST- 2004/10/20 09:00 [entrez]
PST - ppublish
SO  - Int J Mol Med. 2004 Nov;14(5):837-42.