Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Meibergdreef 9, Amsterdam, the Netherlands.
Amsterdam UMC, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Meibergdreef 9, Amsterdam, the Netherlands.
J Hepatol. 2021 Feb;74(2):428-441. doi: 10.1016/j.jhep.2020.10.010. Epub 2020 Oct 24.
Many epithelia secrete bicarbonate-rich fluid to generate flow, alter viscosity, control pH and potentially protect luminal and intracellular structures from chemical stress. Bicarbonate is a key component of human bile and impaired biliary bicarbonate secretion is associated with liver damage. Major efforts have been undertaken to gain insight into acid-base homeostasis in cholangiocytes and more can be learned from analogous secretory epithelia. Extrahepatic examples include salivary and pancreatic duct cells, duodenocytes, airway and renal epithelial cells. The cellular machinery involved in acid-base homeostasis includes carbonic anhydrase enzymes, transporters of the solute carrier family, and intra- and extracellular pH sensors. This pH-regulatory system is orchestrated by protein-protein interactions, the establishment of an electrochemical gradient across the plasma membrane and bicarbonate sensing of the intra- and extracellular compartment. In this review, we discuss conserved principles identified in analogous secretory epithelia in the light of current knowledge on cholangiocyte physiology. We present a framework for cholangiocellular acid-base homeostasis supported by expression analysis of publicly available single-cell RNA sequencing datasets from human cholangiocytes, which provide insights into the molecular basis of pH homeostasis and dysregulation in the biliary system.
许多上皮细胞分泌富含碳酸氢盐的液体以产生流动、改变粘度、控制 pH 值，并可能保护腔道和细胞内结构免受化学应激。碳酸氢盐是人类胆汁的关键成分，胆汁碳酸氢盐分泌受损与肝损伤有关。人们已经做出了巨大努力来深入了解胆管细胞中的酸碱稳态，并且可以从类似的分泌上皮细胞中学到更多知识。肝外的例子包括唾液腺和胰腺导管细胞、十二指肠细胞、气道和肾上皮细胞。参与酸碱稳态的细胞机制包括碳酸酐酶酶、溶质载体家族的转运体以及细胞内和细胞外的 pH 传感器。这个 pH 调节系统是通过蛋白质-蛋白质相互作用、跨质膜建立电化学梯度以及细胞内和细胞外腔的碳酸氢盐感应来协调的。在这篇综述中，我们根据当前对胆管细胞生理学的了解，讨论了在类似分泌上皮细胞中发现的保守原则。我们提出了一个支持胆管细胞酸碱稳态的框架，该框架基于人类胆管细胞公开的单细胞 RNA 测序数据集的表达分析，这些数据提供了对胆汁系统中 pH 稳态和失调的分子基础的深入了解。
