RGD Reference Report - Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats. - Rat Genome Database

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

Authors: Tsuruta, S  Nakamuta, M  Enjoji, M  Kotoh, K  Hiasa, K  Egashira, K  Nawata, H 
Citation: Tsuruta S, etal., Int J Mol Med. 2004 Nov;14(5):837-42.
RGD ID: 8549576
Pubmed: PMID:15492853   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Cirrhosis treatmentIMP 8549576 RGD 
Experimental Liver Cirrhosis treatmentISOCCL2 (Homo sapiens)8549576; 8549576human gene in rat modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens

Additional Information