出版社：American Society for Biochemistry and Molecular Biology
摘要：C57L mice are susceptible and AKR mice are resistant to gallstoneformation. We studied in male mice of both strains gallbladderhistopathology, cholecystokinin-induced emptying, and concentratingfunction at 0, 14, 28, and 56 days on a lithogenic diet. Gallbladderwall thickness increased on the diet, with stromal granulocyteinfiltration, progressive fibrosis, edema, and epithelial cellindentation, particularly in C57L. Strong basal cholecystokininoctapeptide-induced gallbladder emptying (70% of fasting volumes)occurred in both strains, but fasting gallbladder volumes weresignificantly larger in C57L (14.8 ± 2.2 µl vs.8.8 ± 1.0 µl). On the diet, fasting volumes increasedexclusively in C57L (28.6 ± 2.9 µl on day 56),with progressively decreased emptying (27% of fasting volumeson day 56). Gallbladder emptying remained normal in AKR. Gallbladderconcentrating function decreased on the lithogenic diet (especiallyin C57L), coinciding with decreased aquaporin-1 (AQP1) and AQP8expression at the mRNA and protein levels. In additional experiments,similar downregulation of AQP1 and AQP8 mRNA expression occurredin farnesoid X receptor (FXR)-deficient mice after 1 week onthe lithogenic diet, without any difference from correspondingwild-type mice. In conclusion, during murine lithogenesis, alteredgallbladder histology is associated with impaired motility,reduced concentrating function, and decreased AQP1 and AQP8expression, the latter without the involvement of the FXR.Supplementary key words aquaporin • cholesterol • farnesoid X receptor • gallbladder emptying • water channel
Abbreviations: CCK, cholecystokinin octapeptide; FXR, farnesoid X receptor
