RGD Reference Report - Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease. - Rat Genome Database

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Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease.

Authors: Marsillach, J  Camps, J  Ferre, N  Beltran, R  Rull, A  Mackness, B  Mackness, M  Joven, J 
Citation: Marsillach J, etal., BMC Gastroenterol. 2009 Jan 14;9:3.
RGD ID: 2307001
Pubmed: PMID:19144177   (View Abstract at PubMed)
PMCID: PMC2632645   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-230X-9-3   (Journal Full-text)

BACKGROUND: Paraoxonase-1 (PON1) is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1). We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved. METHODS: CCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured. RESULTS: High levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARdelta expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005) and between PON1 and the amount of activated stellate cells (P = 0.001). CONCLUSION: Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Cirrhosis  ISOCcl2 (Rattus norvegicus)2307001; 2307001 RGD 
Experimental Liver Cirrhosis  IEP 2307001 RGD 

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