Bile acid interactions with cholangiocytes

Cholangiocytes 在他们的顶端的膜暴露于胆汁酸的高集中。为胆汁酸的选择 transporter，顶端的钠胆汁酸 Cotransporter (ASBT )( 也叫作 Ibat；基因名字 Slc10a2 ) 在 cholangiocyte 上是局部性的顶端的膜。在 basolateral 膜上，四个运输系统被识别了(t-ASBT，多药抵抗(MDR ) 3，一个未辩别出的阴离子 exchanger 系统和器官的溶质 transporter (Ost ) 异侧 transporter， Ostalpha-Ostbeta。一起，这些单向性地搬运 ers 从管的胆汁的行动胆汁酸到发行量。cholangiocytes 吸收的胆汁酸为重新分泌物经由仙子胆管丛再循环回到 hepatocytes 进胆汁。这再循环在 hepatocytes 和 cholangiocytes 之间的胆汁酸被叫作 cholehepatic 分流小径。最近的研究建议 cholehepatic 分流小径可以由于额外的肝的阻塞在胆汁酸并且到改编的全面肝胆管运输作出贡献到长期的胆汁郁积。ASBT 被腺苷 3' 尖锐地调整， 5'-monophosphate (营地) 依赖者易位到顶端的膜并且由 phosphorylation 依赖的 ubiquitination 和 proteasome 降级。ASBT 被变化长期地响应胆汁的胆汁酸集中和煽动性的 cytokines 在基因表示调整。cholangiocyte ASBT 的另一潜在的功能是允许 cholangiocytes 取样胆汁的胆汁酸以便激活细胞内部的表明小径。在细胞内部的钙，蛋白质激酶 C (PKC ) ， phosphoinositide 3-kinase (PI3K ) ，激活 mitogen 的蛋白质(地图) 激酶和细胞外的调整信号的蛋白质激酶(英皇家空军之阶级最低之兵) 的胆汁酸扳机变化细胞内部的信号。胆汁酸显著地改变 cholangiocyte 分泌物，增长和幸存。不同胆汁酸在 cholangiocyte 上有微分效果细胞内部发信号，并且在一些例子，扳机反对在 cholangiocyte 上完成分泌物，增长和幸存。在这些之上基于概念和观察， cholangiocyte 被建议了是为在肝的胆汁酸的原则目标房间。

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, Ostα- Ostβ. 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）, mitogenactivated protein （MAP） kinase and extracellular signalregulated 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.