The α researchers used cDNA array analysis to provide novel insights into the pathogenesis of primary biliary cirrhosis (PBC)-related liver injury.
The findings were reported in the October issue of Gut.
Utilizing cDNA arrays of 874 genes, PBC was compared with primary sclerosing cholangitis (PSC)-associated cirrhosis and non-diseased liver.
Differential expression of 10 genes was confirmed by real time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
Array analysis identified many differentially expressed genes that are important in inflammation, fibrosis, proliferation, signaling, apoptosis, and oxidative stress.
PBC was associated with increased expression of both Th1- and Th2-type molecules of the immune response.
|Pathways implicated in PBC:|
- Intrahepatic inflammation
Fibrosis-related gene expression featured upregulation of connective tissue growth factor and transforming growth factor beta3.
Many more apoptosis-associated molecules exhibited increased expression. This was consistent with apoptosis in PSC-associated cirrhosis being a more active and regulated process than in PBC.
Increased expression of many genes of the Wnt and notch pathways was observed. This implicated these highly conserved and linked pathways in PBC pathogenesis.
The observed increases in expression of c-jun, c-myc, and c-fos-related antigen 1 were consistent with increased Wnt pathway activity in PBC.
Differential expression of four components of the Wnt pathway - Wnt-5a, Wnt-13, FRITZ, and beta-catenin - was confirmed by quantitative RT-PCR.
Author N. A. Shackel, of the Royal Prince Alfred Hospital and the University of Sydney, concluded on behalf of the group, "Many genes implicated in intrahepatic inflammation, fibrosis, and regeneration were upregulated in PBC.
"In particular, increased expression of a number of Drosophila homologues was seen in PBC."