PDF(Pubmed)
Abstract：
Hepatocytes produce bile components and secrete them into a lumen, known as a bile canaliculus, that is formed by the apical membranes of adjoining hepatocytes. Bile canaliculi merge to form tubular structures that subsequently connect to the canal of Hering and larger intra- and extrahepatic bile ducts formed by cholangiocytes, which modify bile and enable flow through the small intestine. The major functional requirements for bile canaliculi are the maintenance of canalicular shape to preserve the blood-bile barrier and regulation of bile flow. These functional requirements are mediated by functional modules, primarily transporters, the cytoskeleton, cell-cell junctions, and mechanosensing proteins. I propose here that bile canaliculi behave as robust machines whereby the functional modules act in a coordinated manner to perform the multistep task of maintaining canalicular shape and bile flow. Cholestasis, the general term for aberrant bile flow, stems from drug/toxin-induced or genetic dysregulation of one or more of the protein components in the functional modules. Here, I discuss the interactions between components of the various functional modules in bile canaliculi and describe how these functional modules regulate canalicular morphology and function. I use this framework to provide a perspective on recent studies of bile canalicular dynamics.
摘要：
肝细胞产生胆汁成分并分泌到管腔中，被称为胆管，由邻接肝细胞的顶膜形成。胆管合并形成管状结构，随后连接到Hering管和由胆管细胞形成的较大的肝内和肝外胆管，它可以改变胆汁并使其流向小肠。胆小管的主要功能要求是维持小管形状以保持血胆屏障和调节胆汁流量。这些功能需求由功能模块介导，主要是运输商,细胞骨架，细胞-细胞连接，和机械传感蛋白。在这里，我建议胆小管表现为坚固的机器，从而使功能模块以协调的方式发挥作用，以执行维持小管形状和胆汁流量的多步骤任务。胆汁淤积,异常胆汁流量的总称，源于功能模块中的一种或多种蛋白质组分的药物/毒素诱导或遗传失调。这里,我讨论了胆小管中各种功能模块的成分之间的相互作用，并描述了这些功能模块如何调节小管的形态和功能。我使用这个框架为最近的胆管动力学研究提供了一个视角。
