Cholangiocyte bile salt transporters in cholesterol gallstone-susceptible and resistant inbred mouse strains.
OBJECTIVE
We investigated the dietary and gender influences on the expression and functionality of cholangiocyte bile salt transporters and development of biliary hyperplasia in cholesterol gallstone-susceptible C57L/J and resistant AKR/J mice.


METHODS
C57L and AKR mice were fed chow, a lithogenic diet, or a cholic acid-containing diet for 14 days. Expression of cholangiocyte bile salt transporter proteins ASBT (SLC10A2), ILBP (FABP6), and MRP3 (ABCC3) were studied by Western blot analysis. Taurocholate uptake studies were performed using microperfusion of isolated bile duct units. The pre- and post-perfusion taurocholate concentrations were analyzed by high performance liquid chromatography. Biliary proliferation in liver sections was scored.


RESULTS
The lithogenic diet induced ductular proliferation in C57L mice. On chow, SLC10A2 and ABCC3 were overexpressed in male and female C57L compared to AKR mice. A lithogenic diet reduced the expressions of FABP6 in both male and female C57L mice, SLC10A2 in female C57L mice, and ABCC3 in male C57L mice. These alterations in transporter expressions were not associated with changes in taurocholate uptake. The lithogenic diet induced biliary hyperplasia and reduced bile salt transporter expressions in C57L mice.


CONCLUSIONS
Although bile salt uptake was not increased in the bile duct unit, we speculate that the biliary hyperplasia on the lithogenic diet may lead to an increase in intrahepatic bile salt recycling during cholesterol cholelithogenesis.
Liu
Julia J
JJ
Division of Gastroenterology, Department of Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada. julia.liu@ualberta.ca
Glickman
Jonathan N
JN
Masyuk
Anatoliy I
AI
Larusso
Nicholas F
NF
D000818:Animals; D001652:Bile Ducts / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D042882:Gallstones / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005768:Gastrointestinal Hormones / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D012737:Sex Factors; D013045:Species Specificity; D027981:Symporters / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism*
D002791:Cholesterol, Dietary; D050556:Fatty Acid-Binding Proteins; D005768:Gastrointestinal Hormones; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; D013656:Taurocholic Acid; C000606532:Fabp6 protein, mouse; C057275:fatty acid-binding protein 6; C071908:sodium-bile acid cotransporter; C114462:multidrug resistance-associated protein 3