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Gene expression profiles reflect sclerosing cholangitis activity in abcb4 (-/-) mice
Karl E Nakken1, Stale Nygard, Terese K Haaland
1Institute for Experimental Medical Research, Ullevål University Hospital and University of Oslo, Oslo, Norway. k.e.nakken@medisin.uio.no
Scandinavian Journal of Gastroenterology
|September 12, 2008
Summary
Gene transcription patterns in mice with sclerosing cholangitis (SC) reflect disease activity. Dietary interventions altering SC in Abcb4 (-/-) mice showed parallel changes in gene expression related to inflammation and fibrosis.
Area of Science:
- Hepatology and molecular biology
- Gastroenterology
- Immunology
Background:
- Abcb4 (-/-) mice develop sclerosing cholangitis (SC) with altered bile composition and hepatic gene transcription.
- SC involves hepatic inflammation, tissue remodeling, and fibrosis, with gene expression patterns potentially reflecting disease activity.
Purpose of the Study:
- To test if hepatic gene transcription rates correlate with sclerosing cholangitis (SC) activity in Abcb4 (-/-) mice.
- To investigate the impact of dietary cholic acid (CA) and ursodeoxycholic acid (UDCA) on SC activity and associated gene expression.
Main Methods:
- Differential hepatic gene transcription was analyzed using cDNA microarrays in Abcb4 (-/-) mice fed CA (high SC activity) or UDCA (low SC activity) diets.
- Real-time polymerase chain reaction (PCR) verified transcription of selected genes.
- Liver pathology was assessed via histopathology scoring.
Main Results:
- CA-fed mice exhibited higher histopathology scores (inflammation, fibrosis) than UDCA-fed mice.
- cDNA microarray revealed significant differences in gene upregulation between CA-fed (1582 genes) and UDCA-fed (573 genes) groups.
- Transcription of key genes involved in inflammation (e.g., Ccl2, Nfkappab1) and fibrosis (e.g., Tgfbeta1, Col1a1) paralleled SC activity.
Conclusions:
- The number and activity of differentially transcribed genes related to inflammation, remodeling, and fibrosis correlate with SC disease activity in Abcb4 (-/-) mice.
- Hepatic gene transcription profiles can serve as a biomarker for gauging SC disease severity.
