Another research
project we are exploring regulation of transcription by bile acids
in HepG2 cells. A recombinant cell line (human hepatocarcinoma
HepG2) is used for assessing bile acids ability of activating the
Farnesoid receptor (FXR) is co-transfected with two plasmids. The
first bears the FXR. sequence to cause the cells to over-express the
receptor; the second vector plasmid contains a portion of the I-BABP
promoter and the firefly luciferase sequence as a reporter gene
(I-BABP-Luc), so that the activity of FXR agonists or antagonists
can be assessed by the luciferase expression. This system is
utilized for the screening of natural and synthetic bile acids and
could contribute to bile acid structure-activity relationship
studies and facilitate a rational approach to the development of new
drugs. It should be predictive of human pathophysiological
conditions, being based on human cells, and it is rapid to carry out
in comparison to animal-based tests, thus allowing the screening of
many compounds.
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