Gallbladder histopathology during murine gallstone formation: Relation to motility and concentrating function

Karel J. Van Erpecum, David Q H Wang, Antonio Moschetta, Domenico Ferri, Maria Svelto, Piero Portincasa, Jan Jaap Hendrickx, Marguérite Schipper, Giuseppe Calamita

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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 μl vs. 8.8 ± 1.0 ml). On the diet, fasting volumes increased exclusively in C57L (28.6 ± 2.9 μl 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.

Original languageEnglish (US)
Pages (from-to)32-41
Number of pages10
JournalJournal of Lipid Research
Volume47
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Gallstones
Nutrition
Gallbladder
Aquaporin 1
Diet
Fasting
Gallbladder Emptying
Inbred AKR Mouse
Sincalide
Messenger RNA
Histology
Cholecystokinin
Indentation
Infiltration
Granulocytes
Edema
Fibrosis
Down-Regulation
Epithelial Cells
Proteins

Keywords

  • Aquaporin
  • Cholesterol
  • Farnesoid X receptor
  • Gallbladder emptying
  • Water channel

ASJC Scopus subject areas

  • Endocrinology

Cite this

Van Erpecum, K. J., Wang, D. Q. H., Moschetta, A., Ferri, D., Svelto, M., Portincasa, P., ... Calamita, G. (2006). Gallbladder histopathology during murine gallstone formation: Relation to motility and concentrating function. Journal of Lipid Research, 47(1), 32-41. https://doi.org/10.1194/jlr.M500180-JLR200

Gallbladder histopathology during murine gallstone formation : Relation to motility and concentrating function. / Van Erpecum, Karel J.; Wang, David Q H; Moschetta, Antonio; Ferri, Domenico; Svelto, Maria; Portincasa, Piero; Hendrickx, Jan Jaap; Schipper, Marguérite; Calamita, Giuseppe.

In: Journal of Lipid Research, Vol. 47, No. 1, 01.2006, p. 32-41.

Research output: Contribution to journalArticle

Van Erpecum, KJ, Wang, DQH, Moschetta, A, Ferri, D, Svelto, M, Portincasa, P, Hendrickx, JJ, Schipper, M & Calamita, G 2006, 'Gallbladder histopathology during murine gallstone formation: Relation to motility and concentrating function', Journal of Lipid Research, vol. 47, no. 1, pp. 32-41. https://doi.org/10.1194/jlr.M500180-JLR200
Van Erpecum, Karel J. ; Wang, David Q H ; Moschetta, Antonio ; Ferri, Domenico ; Svelto, Maria ; Portincasa, Piero ; Hendrickx, Jan Jaap ; Schipper, Marguérite ; Calamita, Giuseppe. / Gallbladder histopathology during murine gallstone formation : Relation to motility and concentrating function. In: Journal of Lipid Research. 2006 ; Vol. 47, No. 1. pp. 32-41.
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abstract = "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 μl vs. 8.8 ± 1.0 ml). On the diet, fasting volumes increased exclusively in C57L (28.6 ± 2.9 μl 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.",
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