Down-regulation of Wnt signaling during apoptosis of human hepatic stellate cells.

BACKGROUND/AIMS: Hepatic stellate cell apoptosis may play a key role in inhibition of fibrotic hepatic injury. To understand the gene expression profiles of human hepatic stellate cell apoptosis, the global transcript levels in curcumin-induced apoptotic human telomerase reverse transcriptase hepatic stellate cells were analyzed with microarrays.

METHODOLOGY

19K human oligonucleotide microarrays were performed to obtain the gene expression profiles associated with apoptosis in human hepatic stellate cells. The microarray data were verified by real time quantitative PCR and expression of the components of apoptosis and Wnt signaling was analyzed by Western blot.

RESULTS

The apoptosis pathway components, BAX (BCL2-associated X protein) and FLIP (CASP8 and FADD-like apoptosis regulator), had increased or decreased expression in the microarray data, the findings of which the protein levels were consistent. The Wnt signaling pathway components, AXIN2 and FRA1 (FOS-like antigen 1), showed a decreasing expression in the time course microarrays at the protein level.

CONCLUSION

Our data show various gene expression profiles during apoptosis of human telomerase reverse transcriptase hepatic stellate cells, especially those involved in the apoptosis and Wnt signaling pathways, and demonstrate that the activation of the Wnt signaling pathway is inhibited in curcumin-induced apoptotic human telomerase reverse transcriptase hepatic stellate cells.