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Biology Articles » Anatomy & Physiology » Bile acid interactions with cholangiocytes

Abstract
- Bile acid interactions with cholangiocytes

Bile acid interactions with cholangiocytes
 
Xuefeng Xia1, Heather Francis2, Shannon Glaser3, Gianfranco Alpini4, Gene LeSage5
 
1University of Texas at Houston Medical School, Houston, TX, United States
2Division of Research and Education, Scott & White Hospital and The Texas A&M University System Health Science Center, College of Medicine, Temple, TX, United States
3Department of Medicine, Division of Research and Education, Scott & White Hospital and The Texas A&M University System Health Science Center, College of Medicine, Temple, TX, United States
4Central Texas Veterans Health Care System, and Department of Medicine and Systems Biology and Translational Medicine, United States
 
Supported by a NIH grant DK54208 to Gene LeSage, and a VA Research Scholar Award, a VA Merit Award and the NIH grants DK58411 and DK062975 to Gianfranco Alpini
Correspondence to: 5Gene LeSage, MD, Professor of Medicine, University of Texas Houston Medical School, 6431 Fannin Street, MSB 4.234, Houston TX 77030, United States. gene.lesage@uth.tmc.edu
 
 
Abstract
 
Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2) is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3, an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, Osta-Ostb. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliary plexus back to hepatocytes for re-secretion into bile. This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5’-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines. Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogen-activated protein (MAP) kinase and extracellular signal-regulated protein kinase (ERK) intracellular signals. Bile acids significantly alter cholangiocyte secretion, proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals, and in some instances trigger opposing effects on cholangiocyte secretion, proliferation and survival. Based upon these concepts and observations, the cholangiocyte has been proposed to be the principle target cell for bile acids in the liver.

Key words: Cholangiocytes; Bile acid; Liver

Source: World J Gastroenterol 2006; 12(22): 3553-3563

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