Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function.
C57L mice are susceptible and AKR mice are resistant to gallstone formation. We studied in male mice of both strains gallbladder histopathology, cholecystokinin-induced emptying, and concentrating function at 0, 14, 28, and 56 days on a lithogenic diet. Gallbladder wall thickness increased on the diet, with stromal granulocyte infiltration, progressive fibrosis, edema, and epithelial cell indentation, particularly in C57L. Strong basal cholecystokinin octapeptide-induced gallbladder emptying (70% of fasting volumes) occurred in both strains, but fasting gallbladder volumes were significantly larger in C57L (14.8 +/- 2.2 microl vs. 8.8 +/- 1.0 microl). On the diet, fasting volumes increased exclusively in C57L (28.6 +/- 2.9 microl on day 56), with progressively decreased emptying (27% of fasting volumes on day 56). Gallbladder emptying remained normal in AKR. Gallbladder concentrating function decreased on the lithogenic diet (especially in C57L), coinciding with decreased aquaporin-1 (AQP1) and AQP8 expression at the mRNA and protein levels. In additional experiments, similar downregulation of AQP1 and AQP8 mRNA expression occurred in farnesoid X receptor (FXR)-deficient mice after 1 week on the lithogenic diet, without any difference from corresponding wild-type mice. In conclusion, during murine lithogenesis, altered gallbladder histology is associated with impaired motility, reduced concentrating function, and decreased AQP1 and AQP8 expression, the latter without the involvement of the FXR.
van Erpecum
Karel J
KJ
Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands. k.j.vanerpecum@azu.nl
Wang
David Q-H
DQ
Moschetta
Antonio
A
Ferri
Domenico
D
Svelto
Maria
M
Portincasa
Piero
P
Hendrickx
Jan-Jaap
JJ
Schipper
Marguérite
M
Calamita
Giuseppe
G
D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics; D020346:Aquaporins / Q000235:genetics; D001483:Base Sequence; D001646:Bile / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D005704:Gallbladder / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D016473:Gallbladder Emptying / Q000187:drug effects; D042882:Gallstones / Q000209:etiology* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D015870:Gene Expression; D007473:Ion Channels / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology
C496021:Aqp1 protein, mouse; D020346:Aquaporins; D004041:Dietary Fats; D007473:Ion Channels; D012333:RNA, Messenger; C108330:aquaporin 8; D051398:Aquaporin 1; D012844:Sincalide