Cholesterol Gallstone Disease: Focusing on the Role of Gallbladder

Overview

Journal Lab Invest

Specialty Pathology

Date 2014 Dec 16

PMID 25502177

Citations 19

Authors

Yongsheng Chen

Jing Kong

Shuodong Wu

Affiliations

Soon will be listed here.

Abstract

Gallstone disease (GSD) is one of the most common biliary tract diseases worldwide in which both genetic and environmental factors have roles in its pathogenesis. Biliary cholesterol supersaturation from metabolic defects in the liver is traditionally seen as the main pathogenic factor. Recently, there have been renewed investigative interests in the downstream events that occur in gallbladder lithogenesis. This article focuses on the role of the gallbladder in the pathogenesis of cholesterol GSD (CGD). Various conditions affecting the crystallization process are discussed, such as gallbladder motility, concentrating function, lipid transport, and an imbalance between pro-nucleating and nucleation inhibiting proteins.

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References

Lavoie B, Nausch B, Zane E, Leonard M, Balemba O, Bartoo A . Disruption of gallbladder smooth muscle function is an early feature in the development of cholesterol gallstone disease. Neurogastroenterol Motil. 2012; 24(7):e313-24. PMC: 3378777. DOI: 10.1111/j.1365-2982.2012.01935.x. View

Shi Q, Hou Y, Hou J, Pan P, Liu Z, Jiang M . Glycyrrhetic acid synergistically enhances β₂-adrenergic receptor-Gs signaling by changing the location of Gαs in lipid rafts. PLoS One. 2012; 7(9):e44921. PMC: 3459958. DOI: 10.1371/journal.pone.0044921. View

Chen Q, Amaral J, Biancani P, Behar J . Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity. Gastroenterology. 1999; 116(3):678-85. DOI: 10.1016/s0016-5085(99)70190-3. View

Miquel J, Moreno M, Amigo L, Molina H, Mardones P, Wistuba I . Expression and regulation of scavenger receptor class B type I (SR-BI) in gall bladder epithelium. Gut. 2003; 52(7):1017-24. PMC: 1773711. DOI: 10.1136/gut.52.7.1017. View

Crajoinas R, Lessa L, Carraro-Lacroix L, Davel A, Pacheco B, Rossoni L . Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Renal Physiol. 2010; 299(4):F872-81. DOI: 10.1152/ajprenal.00654.2009. View

Bjorck S, Jansson R, Svanvik J . The concentrating function of the feline gallbladder after truncal vagotomy. Acta Chir Scand. 1984; 150(5):393-7. View

Bazzini C, Botta G, Meyer G, Baroni M, Paulmichl M . The presence of NHE1 and NHE3 Na+-H+ exchangers and an apical cAMP-independent Cl- channel indicate that both absorptive and secretory functions are present in calf gall bladder epithelium. Exp Physiol. 2001; 86(5):571-83. DOI: 10.1113/eph8602267. View

Maurer K, Carey M, Fox J . Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology. 2008; 136(2):425-40. PMC: 2774219. DOI: 10.1053/j.gastro.2008.12.031. View

Radberg G, Svanvik J . Influence of pregnancy, oophorectomy and contraceptive steroids on gall bladder concentrating function and hepatic bile flow in the cat. Gut. 1986; 27(1):10-4. PMC: 1433175. DOI: 10.1136/gut.27.1.10. View

10.

Giurgiu D, Roslyn J, Abedin M . Sequential changes in biliary lipids and gallbladder ion transport during gallstone formation. Ann Surg. 1997; 225(4):382-90. PMC: 1190746. DOI: 10.1097/00000658-199704000-00007. View

11.

Matyja A, Gil K, Pasternak A, Sztefko K, Gajda M, Tomaszewski K . Telocytes: new insight into the pathogenesis of gallstone disease. J Cell Mol Med. 2013; 17(6):734-42. PMC: 3823177. DOI: 10.1111/jcmm.12057. View

12.

Pauletzki J, Althaus R, Holl J, Sackmann M, Paumgartner G . Gallbladder emptying and gallstone formation: a prospective study on gallstone recurrence. Gastroenterology. 1996; 111(3):765-71. DOI: 10.1053/gast.1996.v111.pm8780583. View

13.

Cremaschi D, Porta C, Botta G, Bazzini C, Baroni M, Garavaglia M . Apical Na+-Cl- symport in rabbit gallbladder epithelium: a thiazide-sensitive cotransporter (TSC). J Membr Biol. 2000; 176(1):53-65. View

14.

Zen Y, Harada K, Sasaki M, Tsuneyama K, Katayanagi K, Yamamoto Y . Lipopolysaccharide induces overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells: possible key phenomenon of hepatolithiasis. Am J Pathol. 2002; 161(4):1475-84. PMC: 1867307. DOI: 10.1016/S0002-9440(10)64423-9. View

15.

Zhou M, Yang G, Jiao S, Hu C, Mei Y . Cholesterol enhances neuron susceptibility to apoptotic stimuli via cAMP/PKA/CREB-dependent up-regulation of Kv2.1. J Neurochem. 2011; 120(4):502-14. DOI: 10.1111/j.1471-4159.2011.07593.x. View

16.

Narins S, Ramakrishnan R, Park E, Bolno P, Haggerty D, Smith P . Protein kinase C-alpha regulation of gallbladder Na+ transport becomes progressively more dysfunctional during gallstone formation. J Lab Clin Med. 2005; 146(4):227-37. DOI: 10.1016/j.lab.2005.05.008. View

17.

Petersen K, Wehner F, Winterhager J . Na/H exchange at the apical membrane of guinea-pig gallbladder epithelium: properties and inhibition by cyclic AMP. Pflugers Arch. 1985; 405 Suppl 1:S115-20. DOI: 10.1007/BF00581791. View

18.

Moser A, Abedin M, Abedin Z, Roslyn J . Ca2+ calmodulin regulates basal gallbladder absorption. Surgery. 1993; 114(2):300-7. View

19.

Pasternak A, Gajda M, Gil K, Matyja A, Tomaszewski K, Walocha J . Evidence of interstitial Cajal-like cells in human gallbladder. Folia Histochem Cytobiol. 2012; 50(4):581-5. DOI: 10.5603/19673. View

20.

Narins S, Park E, Ramakrishnan R, Garcia F, Diven J, Balin B . Functional characterization of Na(+)/H(+) exchangers in primary cultures of prairie dog gallbladder. J Membr Biol. 2004; 197(2):123-34. DOI: 10.1007/s00232-003-0647-6. View