Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis‪.‬ Medizin - Open Access LMU - Teil 13/22

Background/Aims
The apical sodium dependent bile acid transporter ASBT (SLC10A2) contributes
substantially to the enterohepatic circulation of bile acids by their reabsorption from
the intestine. In the rat, its adaptive regulation was observed in the kidneys,
cholangiocytes and terminal ileum after bile duct ligation. Whether an adaptive
regulation of the human intestinal ASBT exists during obstructive cholestasis is not
known.
Methods
Human ASBT mRNA expression along the intestinal tract was analyzed by real time
PCR in biopsies of 14 control subjects undergoing both gastroscopy and
colonoscopy. Their duodenal ASBT mRNA expression was compared to 20 patients
with obstructive cholestasis. Additionally, in 4 patients with obstructive cholestasis,
duodenal ASBT mRNA expression was measured after reconstitution of bile flow.
Results
Normalized ASBT expression in control subjects was highest (mean arbitrary units±
SEM) in the terminal ileum 1010 ± 330. Low ASBT expression was found in the
colonic segments (8.3±5, 4.9±0.9, 4.8±1.7 and 1.1±0.2, ascending, transverse,
descending, and sigmoid colon, respectively). Duodenal ASBT expression of control
subjects was found with 171.8±20.3 at about four fold higher levels when compared
to 37.9±6.5 (p0.0001) in patients with obstructive cholestasis. Individual ASBT
mRNA expression was inversely correlated with bile acid and bilirubin plasma
concentrations. In 4 cholestatic patients average ASBT mRNA increased from 76±18
before to 113±18 after relief of cholestasis (NS). Immunohistochemical assessment
indicates that ASBT protein is expressed on the apical surface of the duodenal
epithelial cells.
Conclusion
Obstructive cholestasis in humans leads to down-regulation of ASBT mRNA
expression in the distal part of the human duodenum.